NM_024675.4(PALB2):c.2067G>A (p.Ser689=) AND not specified

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Jul 29, 2021
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:: RCV000420216.6

Allele description [Variation Report for NM_024675.4(PALB2):c.2067G>A (p.Ser689=)]

NM_024675.4(PALB2):c.2067G>A (p.Ser689=)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.2067G>A (p.Ser689=)

HGVS:

NC_000016.10:g.23630087C>T
NG_007406.1:g.16271G>A
NM_024675.4:c.2067G>AMANE SELECT
NP_078951.2:p.Ser689=
NP_078951.2:p.Ser689=
LRG_308t1:c.2067G>A
LRG_308:g.16271G>A
LRG_308p1:p.Ser689=
NC_000016.9:g.23641408C>T
NM_024675.3:c.2067G>A
p.S689S

Links:

dbSNP: rs371149159

NCBI 1000 Genomes Browser:

rs371149159

Molecular consequence:

NM_024675.4:c.2067G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000518126	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely benign (Jun 15, 2017)	germline	clinical testing	Citation Link,
SCV000919943	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Apr 23, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26283626, 23977390 Citation Link,
SCV002068911	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 29, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000518126

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely benign
(Jun 15, 2017)

germline

clinical testing

Citation Link,

SCV000919943

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Apr 23, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002068911

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jul 29, 2021)

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	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

Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls.

Thompson ER, Gorringe KL, Rowley SM, Wong-Brown MW, McInerny S, Li N, Trainer AH, Devereux L, Doyle MA, Li J, Lupat R, Delatycki MB; LifePool Investigators, Mitchell G, James PA, Scott RJ, Campbell IG.

Breast Cancer Res. 2015 Aug 19;17(1):111. doi: 10.1186/s13058-015-0627-7.

PubMed [citation]

PMID:: 26283626
PMCID:: PMC4539664

Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore.

Phuah SY, Lee SY, Kang P, Kang IN, Yoon SY, Thong MK, Hartman M, Sng JH, Yip CH, Taib NA, Teo SH.

PLoS One. 2013;8(8):e73638. doi: 10.1371/journal.pone.0073638.

PubMed [citation]

PMID:: 23977390
PMCID:: PMC3748013

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000518126.4

#	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 likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919943.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: PALB2 c.2067G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was observed with an allele frequency of 3.2e-05 in 246256 control chromosomes (gnomAD). The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 2-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in PALB2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. The variant, c.2067G>A, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Phuah_2013, Thompson_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as benign.

#	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 Genetic Services Laboratory, University of Chicago, SCV002068911.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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