Submissions for variant NM_000059.4(BRCA2):c.3165T>G (p.Asn1055Lys)

dbSNP: rs1064793384

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480925	SCV000565977	uncertain significance	not provided	2015-03-20	criteria provided, single submitter	clinical testing	This variant is denoted BRCA2 c.3165T>G at the cDNA level, p.Asn1055Lys (N1055K) at the protein level, and results in the change of an Asparagine to a Lysine (AAT>AAG). Using alternate nomenclature, this variant would be defined as BRCA2 3393T>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asn1055Lys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Asparagine and Lysine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Asn1055Lys occurs at a position that is not conserved across species and is not located in a known functional domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Asn1055Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color Diagnostics, LLC DBA Color Health	RCV000580969	SCV000683532	uncertain significance	Hereditary cancer-predisposing syndrome	2019-04-25	criteria provided, single submitter	clinical testing
University of Washington Department of Laboratory Medicine, University of Washington	RCV000580969	SCV003851729	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).