Submissions for variant NM_000051.4(ATM):c.785T>A (p.Leu262Ter)

dbSNP: rs864622163

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206320	SCV000259524	pathogenic	Ataxia-telangiectasia syndrome	2022-10-20	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu262*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 219578). For these reasons, this variant has been classified as Pathogenic.
Counsyl	RCV000206320	SCV000793316	likely pathogenic	Ataxia-telangiectasia syndrome	2017-08-10	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000206320	SCV003818707	likely pathogenic	Ataxia-telangiectasia syndrome	2021-12-22	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003462368	SCV004216221	pathogenic	Familial cancer of breast	2023-12-22	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003462368	SCV004933694	pathogenic	Familial cancer of breast	2024-01-11	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Ambry Genetics	RCV004948211	SCV005509594	pathogenic	Hereditary cancer-predisposing syndrome	2024-10-16	criteria provided, single submitter	clinical testing	The p.L262* pathogenic mutation (also known as c.785T>A), located in coding exon 6 of the ATM gene, results from a T to A substitution at nucleotide position 785. This changes the amino acid from a leucine to a stop codon within coding exon 6. This variant has been reported as a pathogenic mutation in an individual with a personal history of breast and endometrial cancer from a cohort of 1191 cancer index patients who underwent clinical evaluation and testing with multigene panels (Chan GHJ et al. Oncotarget, 2018 Jul;9:30649-30660). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.