ClinVar

Description

The ATM p.Ser1905Ilefs*25 variant was identified in 9 of 20562 proband chromosomes (frequency: 0.0004) from individuals or families with Ataxia-Telangiectasia or pancreatic cancer (Becker-Catania 2000, Li 2000, Mitui 2005, Susswein 2015). The variant was also identified in dbSNP (ID: rs1040777064), ClinVar (classified as pathogenic by Invitae, Ambry Genetics, GeneDx, Color and Mendelics Analise Genomica; and as likely pathogenic by Counsyl). The variant was not identified in LOVD 3.0. The variant was not identified in the following databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The c.5712dup variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1905 and leads to a premature stop codon at position 1929. 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.