Submissions for variant NM_000059.4(BRCA2):c.3221G>A (p.Ser1074Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV003586075	SCV004362003	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-28	criteria provided, single submitter	clinical testing	This missense variant replaces serine with asparagine at codon 1074 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with leukemia (PMID: 26886259). 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	RCV003586075	SCV004915393	uncertain significance	Hereditary cancer-predisposing syndrome	2022-10-12	criteria provided, single submitter	clinical testing	The c.3221G>A (p.S1074N) alteration is located in exon 11 (coding exon 10) of the BRCA2 gene. This alteration results from a G to A substitution at nucleotide position 3221, causing the serine (S) at amino acid position 1074 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.