NM_024675.4(PALB2):c.2167_2168del (p.Met723fs) AND Familial cancer of breast

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

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Jan 28, 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:: RCV000123337.22

Allele description

NM_024675.4(PALB2):c.2167_2168del (p.Met723fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.2167_2168del (p.Met723fs)

HGVS:

NC_000016.10:g.23629986_23629987del
NG_007406.1:g.16371_16372del
NM_024675.4:c.2167_2168delMANE SELECT
NP_078951.2:p.Met723fs
LRG_308:g.16371_16372del
NC_000016.10:g.23629986_23629987delAT
NC_000016.9:g.23641307_23641308del
NC_000016.9:g.23641307_23641308delAT
NM_024675.3:c.2167_2168delAT
NM_024675.4:c.2167_2168del
p.M723VFS*21
p.Met723Valfs*21
p.Met723ValfsX21

Links:

dbSNP: rs587776416

NCBI 1000 Genomes Browser:

rs587776416

Molecular consequence:

NM_024675.4:c.2167_2168del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

Recent activity

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Annotated Genomic for Nucleotide (Select 2240200140) (2)
Nucleotide
RW_0609 AND estd203 (26)
dbVar
CMRF35-like molecule 1 isoform X15 [Homo sapiens]
CMRF35-like molecule 1 isoform X15 [Homo sapiens]
gi|2462553280|ref|XP_054171122.1|

Protein
protein LSM14 homolog B isoform X6 [Homo sapiens]
protein LSM14 homolog B isoform X6 [Homo sapiens]
gi|2462579641|ref|XP_054179066.1|

Protein
Uncultured candidate division JS1 bacterium partial 16S rRNA gene, DGGE band NN1...
Uncultured candidate division JS1 bacterium partial 16S rRNA gene, DGGE band NN15
gi|133919459|emb|AM492289.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000166650	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 28, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 17200668, 17200671, 17200672, 24136930, 24448499, 24556926, 25099575, 28492532
SCV000488150	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Pathogenic (Jan 15, 2016)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24448499, 24556926, 25099575 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV001193192	Leiden Open Variation Database	no assertion criteria provided	Pathogenic (May 13, 2019)	germline	curation	PubMed (3) [See all records that cite these PMIDs] 24448499, 24556926, 25099575
SCV002581186	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 14, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003835783	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 5, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004019682	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Mar 31, 2023)	unknown	clinical testing	Citation Link

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Summary from all submissions

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

Citations

PubMed

PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene.

Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D; Breast Cancer Susceptibility Collaboration (UK)., Easton DF, Stratton MR.

Nat Genet. 2007 Feb;39(2):165-7. Epub 2006 Dec 31.

PubMed [citation]

PMID:: 17200668
PMCID:: PMC2871593

Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer.

Reid S, Schindler D, Hanenberg H, Barker K, Hanks S, Kalb R, Neveling K, Kelly P, Seal S, Freund M, Wurm M, Batish SD, Lach FP, Yetgin S, Neitzel H, Ariffin H, Tischkowitz M, Mathew CG, Auerbach AD, Rahman N.

Nat Genet. 2007 Feb;39(2):162-4. Epub 2006 Dec 31.

PubMed [citation]

PMID:: 17200671

See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000166650.14

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Met723Valfs*21) 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 (rs587776416, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 24448499, 24556926, 25099575). ClinVar contains an entry for this variant (Variation ID: 136132). For these reasons, this variant has been classified as Pathogenic.

#	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 Counsyl, SCV000488150.2

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

#	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 Leiden Open Variation Database, SCV001193192.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (3)

Description

Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: 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 MGZ Medical Genetics Center, SCV002581186.1

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

From Baylor Genetics, SCV003835783.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004019682.1

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

Description

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

#	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

Last Updated: May 1, 2024

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