NM_024675.4(PALB2):c.172_175del (p.Gln60fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (9 submissions)
Last evaluated:: Feb 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000212770.40

Allele description

NM_024675.4(PALB2):c.172_175del (p.Gln60fs)

Gene:

PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.172_175del (p.Gln60fs)

HGVS:

NC_000016.10:g.23637886ACAA[1]
NC_000016.9:g.23649207_23649210del
NG_007406.1:g.8465TTGT[1]
NM_024675.4:c.172_175delMANE SELECT
NP_078951.2:p.Gln60fs
LRG_308:g.8465TTGT[1]
NC_000016.9:g.23649207ACAA[1]
NC_000016.9:g.23649207_23649210del
NC_000016.9:g.23649211_23649214del
NM_024675.3:c.172_175delTTGT
NM_024675.4:c.172_175del
NM_024675.4:c.172_175delTTGTMANE SELECT
p.Gln60Argfs*7
p.Gln60ArgfsX7
p.Q60Rfs*7
p.Q60RfsX7

Protein change:

Q60fs

Links:

OMIM: 610355.0007; dbSNP: rs180177143

NCBI 1000 Genomes Browser:

rs180177143

Molecular consequence:

NM_024675.4:c.172_175del - frameshift variant - [Sequence Ontology: SO:0001589]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000149982	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 17, 2019)	germline	clinical testing	Citation Link,
SCV000601740	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Aug 9, 2021)	unknown	clinical testing	PubMed (16) [See all records that cite these PMIDs] 32052252, 31948886, 32339256, 31757951, 31159747, 29052111, 29753700, 21285249, 19264984, 24549055, 24136930, 25330149, 25452441, 22310028, 21618343, 26467025
SCV000704184	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Dec 9, 2016)	germline	clinical testing	Citation Link,
SCV001192937	Leiden Open Variation Database	no assertion criteria provided	Pathogenic (Feb 28, 2020)	germline	curation	PubMed (9) [See all records that cite these PMIDs] 19264984, 21285249, 21618343, 22310028, 24136930, 24549055, 25099575, 25330149, 25452441
SCV001247812	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Feb 1, 2024)	germline	clinical testing	Citation Link,
SCV001446510	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001449955	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 26, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002010978	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 3, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005199037	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 28, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	9	not provided	not provided	1	not provided	clinical testing, curation
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel intronic variant in PALB2 gene and effective prevention of Fanconi anemia in family.

Viakhireva I, Musatova E, Bessonova L, Shcherbatyuk Y, Korobkov S, Zhikriveckaya S, Sofronova Y, Mironova I, Khmelkova D, Konovalov F, Baranova A, Pomerantseva E, Skoblov M.

Fam Cancer. 2020 Jul;19(3):241-246. doi: 10.1007/s10689-020-00165-6. Epub 2020 Feb 12.

PubMed [citation]

PMID:: 32052252

Rare Germline Pathogenic Mutations of DNA Repair Genes Are Most Strongly Associated with Grade Group 5 Prostate Cancer.

Wu Y, Yu H, Li S, Wiley K, Zheng SL, LaDuca H, Gielzak M, Na R, Sarver BAJ, Helfand BT, Walsh PC, Lotan TL, Cooney KA, Black MH, Xu J, Isaacs WB.

Eur Urol Oncol. 2020 Apr;3(2):224-230. doi: 10.1016/j.euo.2019.12.003. Epub 2020 Jan 14.

PubMed [citation]

PMID:: 31948886

See all PubMed Citations (18)

Details of each submission

From GeneDx, SCV000149982.13

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

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)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601740.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (16)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000704184.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Leiden Open Variation Database, SCV001192937.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (9)

Description

Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Alfons Meindl, Marc Tischkowitz.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001247812.21

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

Description

PALB2: PVS1, PS4, PS3:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446510.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001449955.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		6	not provided	not provided	not provided

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002010978.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199037.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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