Submissions for variant NM_000051.4(ATM):c.8644_8647del (p.Ser2882fs)

dbSNP: rs2137083265

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150424	SCV003837968	likely pathogenic	Breast and/or ovarian cancer	2021-06-23	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358510	SCV001554263	pathogenic	not provided		no assertion criteria provided	clinical testing	The ATM p.Ser2882Glnfs*6 variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, or LOVD 3.0 databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.8644_8647del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 2882 and leads to a premature stop codon at position 2887. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the ATM gene are an established mechanism of disease in ATM-associated cancers and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.