NM_000059.4(BRCA2):c.8902A>G (p.Thr2968Ala) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 11, 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:: RCV000557418.12

Allele description [Variation Report for NM_000059.4(BRCA2):c.8902A>G (p.Thr2968Ala)]

NM_000059.4(BRCA2):c.8902A>G (p.Thr2968Ala)

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.8902A>G (p.Thr2968Ala)

Other names:

p.T2968A:ACC>GCC

HGVS:

NC_000013.11:g.32379464A>G
NG_012772.3:g.68985A>G
NM_000059.4:c.8902A>GMANE SELECT
NP_000050.2:p.Thr2968Ala
NP_000050.3:p.Thr2968Ala
LRG_293t1:c.8902A>G
LRG_293:g.68985A>G
LRG_293p1:p.Thr2968Ala
NC_000013.10:g.32953601A>G
NM_000059.3:c.8902A>G
p.T2968A

Protein change:

T2968A

Links:

dbSNP: rs587782021

NCBI 1000 Genomes Browser:

rs587782021

Molecular consequence:

NM_000059.4:c.8902A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000635698	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 11, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26976419, 32850417, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000635698

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 11, 2023)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.

Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE.

J Clin Oncol. 2016 May 1;34(13):1460-8. doi: 10.1200/JCO.2015.65.0747. Epub 2016 Mar 14.

PubMed [citation]

PMID:: 26976419
PMCID:: PMC4872307

Tumor Testing for Somatic and Germline BRCA1/BRCA2 Variants in Ovarian Cancer Patients in the Context of Strong Founder Effects.

Peixoto A, Pinto P, Guerra J, Pinheiro M, Santos C, Pinto C, Santos R, Escudeiro C, Bartosch C, Canário R, Barbosa A, Gouveia A, Petiz A, Abreu MH, Sousa S, Pereira D, Silva J, Teixeira MR.

Front Oncol. 2020;10:1318. doi: 10.3389/fonc.2020.01318.

PubMed [citation]

PMID:: 32850417
PMCID:: PMC7412538

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000635698.8

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

Description

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2968 of the BRCA2 protein (p.Thr2968Ala). This variant is present in population databases (rs587782021, gnomAD 0.006%). This missense change has been observed in individual(s) with BRCA2-related conditions (PMID: 26976419, 32850417). ClinVar contains an entry for this variant (Variation ID: 141798). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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