Submissions for variant NM_000059.4(BRCA2):c.9883C>T (p.Gln3295Ter)

dbSNP: rs80359247

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112819	SCV000301418	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
GeneKor MSA	RCV000238720	SCV000296838	pathogenic	not provided	2020-01-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal at codon 3295 of the BRCA2 protein. It is expected to result in an absent or disrupted protein product. Truncating variants in BRCA2 are known to be pathogenic. The mutation database ClinVar contains entries for this variant (Variation ID: 52911).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112819	SCV000328174	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001184567	SCV001350584	likely pathogenic	Hereditary cancer-predisposing syndrome	2019-09-11	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 27 of the BRCA2 gene, creating a premature translation stop signal in the last coding exon. This variant is also known as 10111C>T and Q3295X in the literature. The mutant transcript is predicted to escape nonsense-mediated decay and be expressed as a truncated protein. This variant is expected to disrupt the RAD51 binding domain that has been reported to be essential for homologous recombination and DNA repair (PMID: 17515903). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in families affected with or at risk for breast and ovarian cancer (PMID: 22762150, 28726806, 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.
Invitae	RCV000496879	SCV001578231	pathogenic	Hereditary breast ovarian cancer syndrome	2022-10-08	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BRCA2 protein in which other variant(s) (p.Tyr3308*, p.Gln3299*) have been determined to be pathogenic (PMID: 8896551, 18097605, 18593900, 18607349, 20104584; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 52911). This premature translational stop signal has been observed in individual(s) with personal and/or family history of breast or ovarian cancer (PMID: 22762150, 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln3295*) in the BRCA2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 124 amino acid(s) of the BRCA2 protein.
Baylor Genetics	RCV003473438	SCV004211942	pathogenic	Familial cancer of breast	2023-09-21	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112819	SCV000145725	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2000-07-07	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496879	SCV000588015	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Laboratory of Urology, Hospital Clinic de Barcelona	RCV003332106	SCV004040605	pathogenic	Malignant tumor of urinary bladder		no assertion criteria provided	research