U.S. flag

An official website of the United States government

NM_000059.4(BRCA2):c.9924C>A (p.Tyr3308Ter) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 17, 2017
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:
RCV000479392.1

Allele description [Variation Report for NM_000059.4(BRCA2):c.9924C>A (p.Tyr3308Ter)]

NM_000059.4(BRCA2):c.9924C>A (p.Tyr3308Ter)

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.9924C>A (p.Tyr3308Ter)
Other names:
10152 C>A
HGVS:
  • NC_000013.11:g.32398437C>A
  • NG_012772.3:g.87958C>A
  • NM_000059.4:c.9924C>AMANE SELECT
  • NP_000050.2:p.Tyr3308Ter
  • NP_000050.3:p.Tyr3308Ter
  • LRG_293t1:c.9924C>A
  • LRG_293:g.87958C>A
  • LRG_293p1:p.Tyr3308Ter
  • NC_000013.10:g.32972574C>A
  • NM_000059.3:c.9924C>A
  • p.Tyr3308X
Protein change:
Y3308*
Links:
dbSNP: rs4987049
NCBI 1000 Genomes Browser:
rs4987049
Molecular consequence:
  • NM_000059.4:c.9924C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000572775GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Jan 17, 2017) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000572775.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted BRCA2 c.9924C>A at the cDNA level and p.Tyr3308Ter (Y3308X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAA), and is predicted to cause loss of normal protein function through protein truncation. Even though this frameshift occurs near the end of the gene and nonsense-mediated decay is not expected to occur, it is significant since the last 111 amino acids are no longer translated causing loss of the NLS2 (Borg 2010). BRCA2 Tyr3308Ter due to an alternate nucleotide substitution (c.9924C>G) at the same position, has been observed in several individuals with Hereditary Breast and Ovarian Cancer (Naseem 2006, Alsop 2012). In addition, functional studies of this truncating variant, including assays measuring sensitivity to DNA damaging agents, homologous recombination, genomic instability and RAD51 focus formation all confirm the pathogenicity of this variant (Hucl 2008, Kuznetsov 2008). Based on currently available evidence, we consider this variant to be pathogenic.

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

Last Updated: Sep 1, 2024