ClinVar Genomic variation as it relates to human health
NM_024675.4(PALB2):c.172_175del (p.Gln60fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_024675.4(PALB2):c.172_175del (p.Gln60fs)
Variation ID: 126623 Accession: VCV000126623.87
- Type and length
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Microsatellite, 4 bp
- Location
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Cytogenetic: 16p12.2 16: 23637886-23637889 (GRCh38) [ NCBI UCSC ] 16: 23649207-23649210 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Aug 25, 2024 Mar 20, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024675.4:c.172_175del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_078951.2:p.Gln60fs frameshift NM_024675.4:c.172_175delTTGT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_024675.3:c.172_175delTTGT NC_000016.10:g.23637886ACAA[1] NC_000016.9:g.23649207ACAA[1] NG_007406.1:g.8465TTGT[1] LRG_308:g.8465TTGT[1] - Protein change
- Q60fs
- Other names
- -
- Canonical SPDI
- NC_000016.10:23637885:ACAAACAA:ACAA
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- loss_of_function_variant Sequence Ontology [SO:0002054]
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PALB2 | - | - |
GRCh38 GRCh37 |
5899 | 5940 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (10) |
criteria provided, multiple submitters, no conflicts
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Mar 20, 2024 | RCV000114496.31 | |
Pathogenic (3) |
criteria provided, single submitter
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Dec 14, 2023 | RCV000114497.11 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 21, 2022 | RCV000116073.22 | |
Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000212770.40 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 11, 2019 | RCV001270993.4 | |
Likely pathogenic (1) |
no assertion criteria provided
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Jul 19, 2021 | RCV001543616.4 | |
Pathogenic (2) |
criteria provided, single submitter
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Jan 2, 2019 | RCV001193414.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 13, 2019 | RCV001781441.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 11, 2022 | RCV002490763.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Jun 01, 2015)
|
criteria provided, single submitter
Method: case-control
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Familial cancer of breast
Cases recruited through familial
(more...)
Affected status: yes
Allele origin:
germline
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Cancer Genetics Laboratory, Peter MacCallum Cancer Centre
Accession: SCV000267958.1
First in ClinVar: May 11, 2016 Last updated: May 11, 2016 |
Number of individuals with the variant: 1
Sex: female
Geographic origin: Australia
|
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Pathogenic
(Dec 09, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000704184.2
First in ClinVar: Dec 26, 2017 Last updated: Dec 15, 2018 |
Sex: mixed
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Pathogenic
(Jan 02, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001362215.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: PALB2 c.172_175delTTGT (p.Gln60ArgfsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: PALB2 c.172_175delTTGT (p.Gln60ArgfsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-05 in 277228 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in PALB2 causing Hereditary Breast and Ovarian Cancer (4e-05 vs 0.00016), allowing no conclusion about variant significance. c.172_175delTTGT has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Hellebrand 2011, Casadei 2011 ,Kraus 2016) and pancreatic cancer (Jones 2009). These data indicate that the variant is very likely to be associated with disease. In addition, a case-control study found this variant to be present at a significantly higher frequency in breast cancer patients than in unaffected controls (OR=5.02; p=0.0016) (Cybulski 2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (9)/likely pathogenic(1). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jun 13, 2019)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group N
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002016517.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pancreatic cancer, susceptibility to, 3
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004242403.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
Criteria applied: PVS1,PS4
Clinical Features:
Neoplasm of the pancreas (present)
Sex: male
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Pathogenic
(Mar 20, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
paternal
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002505617.3
First in ClinVar: Apr 30, 2022 Last updated: Apr 15, 2024 |
Comment:
Criteria applied: PVS1,PS4,PM5_SUP
Clinical Features:
Family history of cancer (present)
Sex: female
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Pathogenic
(Mar 10, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004202018.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Apr 27, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
germline
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Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000840029.1
First in ClinVar: Oct 13, 2018 Last updated: Oct 13, 2018 |
Comment:
A heterozygous c.172_17del (p.Gln60Argfs*7) pathogenic variant in the PALB2 gene was detected in this individual. This variant has been previously described as disease-causing in pancreatic, … (more)
A heterozygous c.172_17del (p.Gln60Argfs*7) pathogenic variant in the PALB2 gene was detected in this individual. This variant has been previously described as disease-causing in pancreatic, breast and ovarian cancer (PMID: 19264984, 27038244, 25959805, 21285249, 21285249, 22310028, 22310028). Therefore, we consider this variant to be pathogenic. (less)
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Pathogenic
(Jan 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
germline
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GeneKor MSA
Accession: SCV000821755.2
First in ClinVar: Oct 10, 2018 Last updated: Mar 25, 2020 |
Comment:
This variation is a deletion of 4 nucleotides from exon 3 of the PALB2 mRNA, causing a frameshift after codon 60 and the creation of … (more)
This variation is a deletion of 4 nucleotides from exon 3 of the PALB2 mRNA, causing a frameshift after codon 60 and the creation of a premature translation stop signal 7 amino acid residues later p.(Gln60Argfs*7). This is expected to result in an absent or disrupted protein product. Truncating mutation in PALB2 gene are known to be pathogenic. The mutation database ClinVar contains multiple entries for this variant (Variation ID: 126623). (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446510.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Breast carcinoma (present) , Endometrial carcinoma (present)
Sex: female
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Pathogenic
(Apr 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449955.1
First in ClinVar: Dec 10, 2020 Last updated: Dec 10, 2020 |
Number of individuals with the variant: 6
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Pathogenic
(Apr 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: yes
Allele origin:
germline
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Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499699.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Pathogenic
(Sep 17, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000149982.13
First in ClinVar: May 14, 2014 Last updated: Apr 17, 2019 |
Comment:
Recurrent variant in Polish and Czech populations (Janatova 2013, Cybulski 2015); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a … (more)
Recurrent variant in Polish and Czech populations (Janatova 2013, Cybulski 2015); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Case control studies suggest this variant is associated with breast and pancreatic cancer (Cybulski 2015, Lener 2016); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Jones 2009, Casadei 2011, Hellebrand 2011, Janatova 2013, Thompson 2015, Kluska 2017, Kraus 2017); This variant is associated with the following publications: (PMID: 26283626, 22310028, 24136930, 30716324, 19264984, 21285249, 25330149, 25959805, 21618343, 27038244, 23935381, 24982446, 28008555, 27488870, 26843898, 27099641, 27616075, 23242139, 26681312, 27757719, 28279176, 28281021, 28454591, 28724667, 28657667, 25452441, 24549055, 29052111, 29753700, 30086788, 30426508, 30322717, 31159747, 30113427, 31312277, 31757951, 29625052, 26689913, 32052252, 31447099, 31948886, 32339256) (less)
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Pathogenic
(Jun 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002580281.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PS4_MOD, PM2_SUP
|
Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Jan 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Fanconi anemia complementation group N Pancreatic cancer, susceptibility to, 3
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002811651.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
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Pathogenic
(Apr 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004019725.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Pathogenic
(Aug 09, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601740.4
First in ClinVar: Mar 08, 2017 Last updated: Jan 06, 2024 |
Comment:
This frameshift variant causes the premature termination of PALB2 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or … (more)
This frameshift variant causes the premature termination of PALB2 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or ovarian cancer, pancreatic cancer, prostate cancer, and medulloblastoma (PMID: 32339256 (2020), 31948886 (2020), 29753700 (2018), 29052111 (2018), 25452441 (2015), 24549055 (2014), and 19264984 (2009)). In addition, it has been reported in an individual with Fanconi Anemia, compound heterozygous with a PALB2 splice variant (PMID: 32052252 (2020)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Dec 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000685897.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 4 nucleotides in exon 3 of the PALB2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 4 nucleotides in exon 3 of the PALB2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 15 individuals affected with breast and/or ovarian cancer (PMID: 21285249, 21618343, 22310028, 24136930, 25099575, 25452441, 26283626, 27616075, 28724667, 29052111), 2 individuals affected with pancreatic cancer (PMID: 19264984, 27038244) and an individual affected with medulloblastoma (PMID: 29753700). This variant also has been reported in a breast cancer case-control study in 40/12529 cases and 10/4702 unaffected individuals (OR = 4.02, 95% CI 1.6 to 16.2) and a breast cancer case-control meta-analysis in 24/60466 cases and 9/53461 unaffected individuals (OR = 2.358, 95%CI 1.096 to 5.074) (PMID: 25959805, 33471991; Leiden Open Variation Database DB-ID PALB2_010002). This variant has been identified in 12/282872 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jan 28, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000290814.11
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln60Argfs*7) in the PALB2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln60Argfs*7) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is present in population databases (rs180177143, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with pancreatic cancer (PMID: 19264984, 21285249, 21618343, 22310028, 24136930, 25959805, 27038244, 27616075). ClinVar contains an entry for this variant (Variation ID: 126623). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247812.21
First in ClinVar: May 12, 2020 Last updated: Aug 04, 2024 |
Comment:
PALB2: PVS1, PS4, PS3:Supporting
Number of individuals with the variant: 3
|
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Pathogenic
(Aug 15, 2017)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000785469.2
First in ClinVar: Jul 14, 2018 Last updated: Jul 14, 2018 |
|
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Pathogenic
(Apr 30, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002530642.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The PABL2 c.172_175del (p.Q60RfsX7) variant has been reported in individuals with breast cancer (PMID:21285249, 21618343, 24136930, 27488870, 30426508, 31312277). This variant has also been reported … (more)
The PABL2 c.172_175del (p.Q60RfsX7) variant has been reported in individuals with breast cancer (PMID:21285249, 21618343, 24136930, 27488870, 30426508, 31312277). This variant has also been reported in individuals with ovarian cancer (PMID:22310028, 30322717,29052111). In a case-control study, this variant showed a strong association with an increased risk of breast cancer (OR=5.02; p=0.0016) (PMID:25959805). This variant causes a frameshift at amino acid 60 that results in premature termination 7 amino acids downstream. At this location, this is predicted to cause nonsense-mediated decay and result in an absent protein (loss of function). Loss of function variants in PALB2 are known to be pathogenic (PMID:25099575). This variant was observed in 1/10368 chromosomes in the Ashkenazi Jewish population and in 10/129184 chromosomes in the European(non-Finnish) population according to the Genome Aggregation Database (http://gnomad.broadinstitute.org). The variant has been reported in ClinVar (Variation ID 126623). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
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Pathogenic
(Dec 09, 2022)
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criteria provided, single submitter
Method: research
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Familial cancer of breast
Affected status: no
Allele origin:
germline
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV002762828.2
First in ClinVar: Dec 17, 2022 Last updated: Feb 25, 2023 |
Comment:
PVS1, PS4_STR
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Pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010978.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
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Pathogenic
(Sep 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000172718.10
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.172_175delTTGT (p.Q60Rfs*7) alteration, located in exon 3 (coding exon 3) of the PALB2 gene, consists of a deletion of 4 nucleotides from position 172 … (more)
The c.172_175delTTGT (p.Q60Rfs*7) alteration, located in exon 3 (coding exon 3) of the PALB2 gene, consists of a deletion of 4 nucleotides from position 172 to 175, causing a translational frameshift with a predicted alternate stop codon after 7 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration has been reported in pancreatic, breast, and ovarian cancer patients, including multiple individuals with family histories significant for PALB2-related cancers (Jones, 2009; Casadei, 2011; Prokofyeva, 2012; Janatova, 2013; Cybulski, 2015; Kluska, 2017; Myszka, 2018). It was also seen in a patient with medulloblastoma (Waszak, 2018). Based on the available evidence, this alteration is classified as pathogenic. (less)
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Pathogenic
(Jun 28, 2023)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199037.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
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risk factor
(Apr 10, 2009)
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no assertion criteria provided
Method: literature only
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PANCREATIC CANCER, SUSCEPTIBILITY TO, 3
Affected status: not provided
Allele origin:
unknown
|
OMIM
Accession: SCV000021461.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In a patient with pancreatic cancer (PNCA3; 613348) whose tumor DNA had previously been sequenced, Jones et al. (2009) found a heterozygous germline deletion of … (more)
In a patient with pancreatic cancer (PNCA3; 613348) whose tumor DNA had previously been sequenced, Jones et al. (2009) found a heterozygous germline deletion of 4 basepairs in the PALB2 gene, TTGT approximately at nucleotide 172 in exon 3, that produced a frameshift at codon 58. The pancreatic cancer had also somatically acquired a transition mutation, a C-to-T transition at a canonical splice site for exon 10 (IVS10+2). (less)
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Pathogenic
(Aug 26, 2022)
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no assertion criteria provided
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV002588982.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
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Pathogenic
(Feb 28, 2020)
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no assertion criteria provided
Method: curation
|
not provided
Affected status: yes
Allele origin:
germline
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Leiden Open Variation Database
Accession: SCV001192937.1
First in ClinVar: Apr 06, 2020 Last updated: Apr 06, 2020 |
Comment:
Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Alfons Meindl, Marc Tischkowitz.
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Pathogenic
(Jun 11, 2019)
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no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV001451805.1
First in ClinVar: Dec 24, 2020 Last updated: Dec 24, 2020 |
Number of individuals with the variant: 3
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
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Likely pathogenic
(Jul 19, 2021)
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no assertion criteria provided
Method: research
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Colorectal cancer
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University School of Medicine.
Accession: SCV001754809.1
First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021 |
Comment:
The Leu58fs variant in PALB2 has been reported in 1 Chinese family with autosomal dominant predisposition in familial colorectal cancer (CRC).
Age: 50-59 years
Sex: male
Ethnicity/Population group: Chinese
Geographic origin: China
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Pathogenic
(Oct 18, 2021)
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no assertion criteria provided
Method: clinical testing
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Pancreatic cancer, susceptibility to, 3
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, University Hospital Schleswig-Holstein
Accession: SCV002029194.1
First in ClinVar: Dec 04, 2021 Last updated: Dec 04, 2021 |
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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loss_of_function_variant
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Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University School of Medicine.
Accession: SCV001754809.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing. | Zhou J | Cancer | 2020 | PMID: 32339256 |
Novel intronic variant in PALB2 gene and effective prevention of Fanconi anemia in family. | Viakhireva I | Familial cancer | 2020 | PMID: 32052252 |
Rare Germline Pathogenic Mutations of DNA Repair Genes Are Most Strongly Associated with Grade Group 5 Prostate Cancer. | Wu Y | European urology oncology | 2020 | PMID: 31948886 |
Functional analysis of genetic variants in the high-risk breast cancer susceptibility gene PALB2. | Boonen RACM | Nature communications | 2019 | PMID: 31757951 |
Allelic variants of breast cancer susceptibility genes PALB2 and RECQL in the Latvian population. | Hilz P | Hereditary cancer in clinical practice | 2019 | PMID: 31312277 |
Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. | Tsaousis GN | BMC cancer | 2019 | PMID: 31159747 |
The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants. | Schubert S | International journal of cancer | 2019 | PMID: 30426508 |
Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. | Waszak SM | The Lancet. Oncology | 2018 | PMID: 29753700 |
Targeted massively parallel sequencing characterises the mutation spectrum of PALB2 in breast and ovarian cancer cases from Poland and Ukraine. | Myszka A | Familial cancer | 2018 | PMID: 29052111 |
Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
PALB2 mutations in BRCA1/2-mutation negative breast and ovarian cancer patients from Poland. | Kluska A | BMC medical genomics | 2017 | PMID: 28279176 |
Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2. | Kraus C | International journal of cancer | 2017 | PMID: 27616075 |
The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome. | Lener MR | Cancer research and treatment | 2017 | PMID: 27488870 |
Do founder mutations characteristic of some cancer sites also predispose to pancreatic cancer? | Lener MR | International journal of cancer | 2016 | PMID: 27038244 |
Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls. | Thompson ER | Breast cancer research : BCR | 2015 | PMID: 26283626 |
Clinical outcomes in women with breast cancer and a PALB2 mutation: a prospective cohort analysis. | Cybulski C | The Lancet. Oncology | 2015 | PMID: 25959805 |
Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. | Couch FJ | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2015 | PMID: 25452441 |
Mutations predisposing to breast cancer in 12 candidate genes in breast cancer patients from Poland. | Cybulski C | Clinical genetics | 2015 | PMID: 25330149 |
Breast-cancer risk in families with mutations in PALB2. | Antoniou AC | The New England journal of medicine | 2014 | PMID: 25099575 |
Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. | Castéra L | European journal of human genetics : EJHG | 2014 | PMID: 24549055 |
The PALB2 gene is a strong candidate for clinical testing in BRCA1- and BRCA2-negative hereditary breast cancer. | Janatova M | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2013 | PMID: 24136930 |
Rare occurrence of PALB2 mutations in ovarian cancer patients from the Volga-Ural region. | Prokofyeva D | Clinical genetics | 2012 | PMID: 22310028 |
Germline mutations in the PALB2 gene are population specific and occur with low frequencies in familial breast cancer. | Hellebrand H | Human mutation | 2011 | PMID: 21618343 |
Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. | Casadei S | Cancer research | 2011 | PMID: 21285249 |
Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. | Jones S | Science (New York, N.Y.) | 2009 | PMID: 19264984 |
Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. | Xia B | Nature genetics | 2007 | PMID: 17200672 |
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. | Reid S | Nature genetics | 2007 | PMID: 17200671 |
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. | Rahman N | Nature genetics | 2007 | PMID: 17200668 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PALB2 | - | - | - | - |
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Text-mined citations for rs180177143 ...
HelpRecord last updated Aug 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.