Submissions for variant NM_000059.4(BRCA2):c.6147_6149del (p.Val2050del)

dbSNP: rs779563857

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480848	SCV000566810	uncertain significance	not provided	2015-06-02	criteria provided, single submitter	clinical testing	This deletion of 3 nucleotides in BRCA2 is denoted c.6147_6149delGGT at the cDNA level and p.Val2050del (V2050del) at the protein level. The normal sequence, with the bases that are deleted in braces, is ATGT[GGT]AAAT. This in frame deletion of a single Valine residue occurs at a position that is not conserved across species and is not located in a known functional domain. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Since in frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider BRCA2 Val2050del to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001218359	SCV001390239	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-10-24	criteria provided, single submitter	clinical testing	This variant, c.6147_6149del, results in the deletion of 1 amino acid(s) of the BRCA2 protein (p.Val2050del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs779563857, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 419177). 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.
Ambry Genetics	RCV002356771	SCV002654920	uncertain significance	Hereditary cancer-predisposing syndrome	2022-10-24	criteria provided, single submitter	clinical testing	The c.6147_6149delGGT variant (also known as p.V2050del) is located in coding exon 10 of the BRCA2 gene. This variant results from an in-frame GGT deletion at nucleotide positions 6147 to 6149. This results in the in-frame deletion of a valine at codon 2050. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV004802052	SCV005424521	uncertain significance	BRCA2-related cancer predisposition	2024-05-14	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of one amino acid, valine at codon 2050, in the BRCA2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has been identified in 3/282356 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.