Submissions for variant NM_000059.4(BRCA2):c.8463dup (p.Ile2822fs)

dbSNP: rs397507988

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000241216	SCV000301279	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000241216	SCV000327896	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000773106	SCV000906580	pathogenic	Hereditary cancer-predisposing syndrome	2023-06-13	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 19 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least two individuals affected with breast and/or ovarian cancer and a suspected hereditary breast and ovarian cancer family (PMID: 22762150, 26306726, 28947987). This variant has been identified in 1/251406 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496662	SCV003442205	pathogenic	Hereditary breast ovarian cancer syndrome	2022-05-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile2822Tyrfs*23) 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). This variant is present in population databases (rs780299355, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with BRCA2-related conditions (PMID: 22762150, 26306726, 28947987). This variant is also known as c.8463_8464insT. ClinVar contains an entry for this variant (Variation ID: 52596). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496662	SCV000587954	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research