Submissions for variant NM_000059.4(BRCA2):c.688A>T (p.Lys230Ter)

dbSNP: rs80358913

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)	RCV000031654	SCV000300346	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.
Ambry Genetics	RCV000221860	SCV000276328	pathogenic	Hereditary cancer-predisposing syndrome	2024-03-21	criteria provided, single submitter	clinical testing	The p.K230* pathogenic mutation (also known as c.688A>T), located in coding exon 8 of the BRCA2 gene, results from an A to T substitution at nucleotide position 688. This changes the amino acid from a lysine to a stop codon within coding exon 8. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Department of Pathology and Molecular Medicine, Queen's University	RCV000496274	SCV000588070	pathogenic	Hereditary breast ovarian cancer syndrome	2017-04-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000221860	SCV001340919	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-07	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 9 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496274	SCV001592846	pathogenic	Hereditary breast ovarian cancer syndrome	2023-06-17	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 38072). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with BRCA2-related conditions (PMID: 10923033, 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys230*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584).
Baylor Genetics	RCV003473206	SCV004212823	pathogenic	Familial cancer of breast	2022-03-29	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031654	SCV000054261	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2010-03-29	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031654	SCV000147491	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2003-12-23	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496274	SCV000587563	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research