Submissions for variant NM_000059.4(BRCA2):c.3799G>A (p.Asp1267Asn)

dbSNP: rs1191600785

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
University of Washington Department of Laboratory Medicine, University of Washington	RCV003158830	SCV003846882	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358210	SCV001553883	uncertain significance	not provided		no assertion criteria provided	clinical testing	The BRCA2 p.Asp1267Asn variant was not identified in the literature nor was it identified in the ClinVar, LOVD 3.0 or in the UMD-LSDB databases. The variant was identified in dbSNP (ID: rs1191600785) as "NA" and in control databases in 1 of 232466 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 1 of 27104 chromosomes (freq: 0.00004), while the variant was not observed in the African, Other, Latino, European, Ashkenazi Jewish, East Asian or Finnish populations. The p.Asp1267 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.