NM_000059.4(BRCA2):c.229A>G (p.Thr77Ala) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 8, 2023
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:: RCV000508014.6

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000566296	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 8, 2023)	germline	clinical testing	Citation Link,
SCV000600506	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jan 28, 2021)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 29684080, 29884841, 26317927, 14647413, 26566862, 18284688, 24835992, 24448238, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000566296

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 8, 2023)

germline

clinical testing

Citation Link,

SCV000600506

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jan 28, 2021)

unknown

clinical testing

PubMed (9)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline PTEN mutations.

Yehia L, Ni Y, Sesock K, Niazi F, Fletcher B, Chen HJL, LaFramboise T, Eng C.

PLoS Genet. 2018 Apr;14(4):e1007352. doi: 10.1371/journal.pgen.1007352.

PubMed [citation]

PMID:: 29684080
PMCID:: PMC5933810

Comprehensive annotation of BRCA1 and BRCA2 missense variants by functionally validated sequence-based computational prediction models.

Hart SN, Hoskin T, Shimelis H, Moore RM, Feng B, Thomas A, Lindor NM, Polley EC, Goldgar DE, Iversen E, Monteiro ANA, Suman VJ, Couch FJ.

Genet Med. 2019 Jan;21(1):71-80. doi: 10.1038/s41436-018-0018-4. Epub 2018 Jun 8.

PubMed [citation]

PMID:: 29884841
PMCID:: PMC6287763

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV000566296.6

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

Description

Observed in individuals with breast cancer (Lee et al., 2008; Yehia et al., 2018; Sandoval et al., 2021); Published functional studies are inconclusive: impaired interaction of BRCA2 with PLK1 (Takaoka et al., 2014; Yata et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 457A>G; This variant is associated with the following publications: (PMID: 24448238, 24835992, 26920070, 26566862, 14647413, 29884841, 32377563, 18284688, 33606809, 31853058, 34598035, 29684080)

#	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		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000600506.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

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

Last Updated: Jun 2, 2024

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