NM_000059.4(BRCA2):c.7955T>G (p.Val2652Gly) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 21, 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:: RCV001211134.8

Allele description [Variation Report for NM_000059.4(BRCA2):c.7955T>G (p.Val2652Gly)]

NM_000059.4(BRCA2):c.7955T>G (p.Val2652Gly)

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.7955T>G (p.Val2652Gly)

Other names:

NP_000050.3:p.Val2652Gly

HGVS:

NC_000013.11:g.32362672T>G
NG_012772.3:g.52193T>G
NM_000059.4:c.7955T>GMANE SELECT
NP_000050.2:p.Val2652Gly
NP_000050.3:p.Val2652Gly
LRG_293t1:c.7955T>G
LRG_293:g.52193T>G
LRG_293p1:p.Val2652Gly
NC_000013.10:g.32936809T>G
NM_000059.3:c.7955T>G
NM_000059.4:c.7955T>G

Protein change:

V2652G

Links:

dbSNP: rs1555286868

NCBI 1000 Genomes Browser:

rs1555286868

Molecular consequence:

NM_000059.4:c.7955T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001382659	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 21, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 34218100, 35464868, 33609447, 28492532
SCV002025835	National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 16, 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

SCV001382659

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 21, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002025835

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 16, 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	yes	2	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

Mutations in BRCA-related breast and ovarian cancer in the South African Indian population: A descriptive study.

Combrink HM, Oosthuizen J, Visser B, Chabilal N, Buccimazza I, Foulkes WD, van der Merwe NC.

Cancer Genet. 2021 Nov;258-259:1-6. doi: 10.1016/j.cancergen.2021.06.002. Epub 2021 Jun 15.

PubMed [citation]

PMID:: 34218100

Prevalence of Clinically Relevant Germline BRCA Variants in a Large Unselected South African Breast and Ovarian Cancer Cohort: A Public Sector Experience.

Van der Merwe NC, Combrink HM, Ntaita KS, Oosthuizen J.

Front Genet. 2022;13:834265. doi: 10.3389/fgene.2022.834265.

PubMed [citation]

PMID:: 35464868
PMCID:: PMC9024354

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001382659.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 2652 of the BRCA2 protein (p.Val2652Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with BRCA2-related cancers (PMID: 34218100, 35464868; external communication). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 489784). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33609447) indicates that this missense variant is expected to disrupt BRCA2 function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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 National Health Laboratory Service, Universitas Academic Hospital and University of the Free State, SCV002025835.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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		2	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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