Submissions for variant NM_000059.4(BRCA2):c.5025TAG[1] (p.Ser1676del)

dbSNP: rs431825326

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000758903	SCV000566515	uncertain significance	not provided	2023-03-03	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 5256_5258delTAG; This variant is associated with the following publications: (PMID: 9002670, 22193408)
Ambry Genetics	RCV000509743	SCV000608021	uncertain significance	Hereditary cancer-predisposing syndrome	2024-11-14	criteria provided, single submitter	clinical testing	The c.5028_5030delTAG variant (also known as p.S1676del) is located in coding exon 10 of the BRCA2 gene. This variant results from an in-frame TAG deletion at nucleotide positions 5028 to 5030. This results in the in-frame deletion of a serine at codon 1676. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000637360	SCV000758815	uncertain significance	Hereditary breast ovarian cancer syndrome	2022-09-20	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 96814). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant, c.5028_5030del, results in the deletion of 1 amino acid(s) of the BRCA2 protein (p.Ser1676del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs763123300, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in BRCA2 in at least one individual (Invitae), which suggests that this variant may not be disease-causing.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000758903	SCV000887834	uncertain significance	not provided	2018-01-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000509743	SCV000906099	uncertain significance	Hereditary cancer-predisposing syndrome	2019-05-03	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000082935	SCV000115009	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2012-05-01	no assertion criteria provided	clinical testing