Submissions for variant NM_000051.4(ATM):c.3349_3355delinsTAAACAT (p.Gln1117_Ala1119delinsTer)

dbSNP: rs1064796055

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484530	SCV000572447	pathogenic	not provided	2022-05-16	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); ATM c.3349C>T p.(Gln1117Ter) was identified in an individual with a personal and family history of breast cancer (Renwick 2006); This variant is associated with the following publications: (PMID: 25525159, 19781682, 16832357)
Ambry Genetics	RCV003168970	SCV003868838	pathogenic	Hereditary cancer-predisposing syndrome	2023-02-13	criteria provided, single submitter	clinical testing	The c.3349_3355delCAAACAGinsTAAACAT pathogenic mutation (also known as p.Q1117*), located in coding exon 22 of the ATM gene, results from an in-frame deletion of CAAACAG and insertion of TAAACAT at nucleotide positions 3349 to 3355. This changes the amino acid from a glutamine to a stop codon within coding exon 22. The ATM p.Q1117* alteration was identified in conjunction with a pathogenic variant in ATM in one individual from the UK diagnosed with ataxia-telangiectasia (Jackson TJ et al. Dev Med Child Neurol, 2016 Jul;58:690-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.