NM_000059.4(BRCA2):c.3578C>T (p.Ala1193Val) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 25, 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:: RCV000082916.5

Allele description [Variation Report for NM_000059.4(BRCA2):c.3578C>T (p.Ala1193Val)]

NM_000059.4(BRCA2):c.3578C>T (p.Ala1193Val)

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.3578C>T (p.Ala1193Val)

HGVS:

NC_000013.11:g.32337933C>T
NG_012772.3:g.27454C>T
NM_000059.4:c.3578C>TMANE SELECT
NP_000050.2:p.Ala1193Val
NP_000050.3:p.Ala1193Val
LRG_293t1:c.3578C>T
LRG_293:g.27454C>T
LRG_293p1:p.Ala1193Val
NC_000013.10:g.32912070C>T
NM_000059.3:c.3578C>T

Protein change:

A1193V

Links:

dbSNP: rs431825310

NCBI 1000 Genomes Browser:

rs431825310

Molecular consequence:

NM_000059.4:c.3578C>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

Recent activity

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ctsf cathepsin F [Danio rerio]
ctsf cathepsin F [Danio rerio]
Gene ID:565588

Gene
Sult2a2 sulfotransferase family 2A, dehydroepiandrosterone (DHEA)-preferring, me...
Sult2a2 sulfotransferase family 2A, dehydroepiandrosterone (DHEA)-preferring, member 2 [Rattus norvegicus]
Gene ID:361510

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000114990	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Uncertain significance (May 1, 2012)	germline	clinical testing
SCV004845187	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Aug 25, 2023)	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

SCV000114990

Sharing Clinical Reports Project (SCRP)

no assertion criteria provided

Uncertain significance
(May 1, 2012)

germline

clinical testing

SCV004845187

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Aug 25, 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	unknown	2	not provided	not provided	108544	not provided	clinical testing
not provided	germline	not provided	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

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 Sharing Clinical Reports Project (SCRP), SCV000114990.3

#	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, SCV004845187.1

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

Description

This missense variant replaces alanine with valine at codon 1193 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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: Sep 29, 2024

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