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NM_000059.4(BRCA2):c.229A>G (p.Thr77Ala) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 31, 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:
RCV000221509.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.229A>G (p.Thr77Ala)]

NM_000059.4(BRCA2):c.229A>G (p.Thr77Ala)

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.229A>G (p.Thr77Ala)
HGVS:
  • NC_000013.11:g.32319238A>G
  • NG_012772.3:g.8759A>G
  • NG_017006.2:g.1126T>C
  • NM_000059.4:c.229A>GMANE SELECT
  • NP_000050.2:p.Thr77Ala
  • NP_000050.3:p.Thr77Ala
  • LRG_293t1:c.229A>G
  • LRG_293:g.8759A>G
  • LRG_293p1:p.Thr77Ala
  • NC_000013.10:g.32893375A>G
  • NM_000059.3:c.229A>G
  • U43746.1:n.457A>G
Nucleotide change:
457A>G
Protein change:
T77A
Links:
dbSNP: rs80358500
NCBI 1000 Genomes Browser:
rs80358500
Molecular consequence:
  • NM_000059.4:c.229A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000275166Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Mar 31, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients.

Lee E, McKean-Cowdin R, Ma H, Chen Z, Van Den Berg D, Henderson BE, Bernstein L, Ursin G.

Breast Cancer Res. 2008;10(1):R19. doi: 10.1186/bcr1865. Epub 2008 Feb 19.

PubMed [citation]
PMID:
18284688
PMCID:
PMC2374975

BRCA2 phosphorylated by PLK1 moves to the midbody to regulate cytokinesis mediated by nonmuscle myosin IIC.

Takaoka M, Saito H, Takenaka K, Miki Y, Nakanishi A.

Cancer Res. 2014 Mar 1;74(5):1518-28. doi: 10.1158/0008-5472.CAN-13-0504. Epub 2014 Jan 21.

PubMed [citation]
PMID:
24448238
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000275166.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The p.T77A variant (also known as c.229A>G), located in coding exon 2 of the BRCA2 gene, results from an A to G substitution at nucleotide position 229. The threonine at codon 77 is replaced by alanine, an amino acid with similar properties. This alteration was identified in a population-based study of early-onset breast cancer diagnoses (Lee E et al. Breast Cancer Res, 2008 Feb;10:R19). This alteration was also detected in a cohort of unrelated Brazilian individuals with breast cancer (Sandoval RL et al. PLoS One, 2021 Mar;16:e0247363). Functional studies indicate that the p.T77A alteration reduces BRCA2-PLK1 binding, which may impair BRCA2 localization and RAD51 recruitment (Takaoka M et al. Cancer Res. 2014 Mar;74(5):1518-28; Yata K et al. Cell Rep. 2014 Jun;7(5):1547-59). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 2, 2024