Submissions for variant NM_000059.4(BRCA2):c.3229GTT[1] (p.Val1078del)

dbSNP: rs1064795381

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000479531	SCV000571132	uncertain significance	not provided	2016-07-28	criteria provided, single submitter	clinical testing	This in-frame deletion of 3 nucleotides in BRCA2 is denoted c.3232_3234delGTT at the cDNA level and p.Val1078del (V1078del) at the protein level. The normal sequence, with the bases that are deleted in braces, is AGTT[GTT]TCTG. This deletion of a single Valine residue occurs at a position where amino acids with properties similar to Valine are tolerated across species and is located in the RAD51 binding domain (Roy 2012). 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 Val1078del to be a variant of uncertain significance.
Color Diagnostics, LLC DBA Color Health	RCV000580575	SCV000683537	uncertain significance	Hereditary cancer-predisposing syndrome	2020-01-14	criteria provided, single submitter	clinical testing	This variant causes the in-frame deletion of one amino acid, Valine 1078, in the BRCA2 protein. 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). 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.
Ambry Genetics	RCV000580575	SCV001180688	uncertain significance	Hereditary cancer-predisposing syndrome	2020-07-01	criteria provided, single submitter	clinical testing	The c.3232_3234delGTT variant (also known as p.V1078del) is located in coding exon 10 of the BRCA2 gene. This variant results from an in-frame GTT deletion at nucleotide positions 3232 to 3234. This results in the in-frame deletion of a valine at codon 1078. This amino acid position is not well 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). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001302139	SCV001491333	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-10-28	criteria provided, single submitter	clinical testing	This variant, c.3232_3234del, results in the deletion of 1 amino acid(s) of the BRCA2 protein (p.Val1078del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). 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: 421821). Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000479531	SCV004219577	uncertain significance	not provided	2023-07-17	criteria provided, single submitter	clinical testing	In the published literature, this variant has been reported in an individual with breast cancer (Bashi, T., et al Turk J Biochem 2020; 45(1): 83-90, https://doi.org/10.1515/tjb-2019-0424). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, we are unable to determine the clinical significance of this variant.