NM_000059.4(BRCA2):c.7783G>T (p.Ala2595Ser) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jun 28, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000113817.12

Allele description [Variation Report for NM_000059.4(BRCA2):c.7783G>T (p.Ala2595Ser)]

NM_000059.4(BRCA2):c.7783G>T (p.Ala2595Ser)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.7783G>T (p.Ala2595Ser)

HGVS:

NC_000013.11:g.32357907G>T
NG_012772.3:g.47428G>T
NM_000059.4:c.7783G>TMANE SELECT
NP_000050.2:p.Ala2595Ser
NP_000050.3:p.Ala2595Ser
LRG_293t1:c.7783G>T
LRG_293:g.47428G>T
LRG_293p1:p.Ala2595Ser
NC_000013.10:g.32932044G>T
NM_000059.3:c.7783G>T
U43746.1:n.8011G>T

Protein change:

A2595S

Links:

dbSNP: rs80359007

NCBI 1000 Genomes Browser:

rs80359007

Molecular consequence:

NM_000059.4:c.7783G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Breast-ovarian cancer, familial, susceptibility to, 2 (BROVCA2)
Synonyms:: Breast-ovarian cancer, familial 2
Identifiers:: MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000147180	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Uncertain significance (Dec 23, 2003)	germline	clinical testing
SCV000297554	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Uncertain significance (Aug 29, 2006)	germline	clinical testing
SCV004845561	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Jun 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35753294, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000147180

Breast Cancer Information Core (BIC) (BRCA2)

no assertion criteria provided

Uncertain significance
(Dec 23, 2003)

germline

clinical testing

SCV000297554

Sharing Clinical Reports Project (SCRP)

no assertion criteria provided

Uncertain significance
(Aug 29, 2006)

germline

clinical testing

SCV004845561

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Jun 28, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	108544	not provided	clinical testing
Western European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline landscape of BRCAs by 7-site collaborations as a BRCA consortium in Turkey.

Bisgin A, Sag SO, Dogan ME, Yildirim MS, Gumus AA, Akkus N, Balasar O, Durmaz CD, Eroz R, Altiner S, Alemdar A, Aliyeva L, Boga I, Cam FS, Dogan B, Esbah O, Hanta A, Mujde C, Ornek C, Ozer S, Rencuzogullari C, Sonmezler O, et al.

Breast. 2022 Oct;65:15-22. doi: 10.1016/j.breast.2022.06.005. Epub 2022 Jun 21.

PubMed [citation]

PMID:: 35753294
PMCID:: PMC9249944

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Breast Cancer Information Core (BIC) (BRCA2), SCV000147180.1

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

From Sharing Clinical Reports Project (SCRP), SCV000297554.1

#	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	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From All of Us Research Program, National Institutes of Health, SCV004845561.1

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

Description

This missense variant replaces alanine with serine at codon 2595 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in an individual with a personal or family history of breast and/or ovarian cancer (PMID: 35753294). This variant has been identified in 1/246168 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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