Submissions for variant NM_000051.4(ATM):c.8397del (p.Gln2800fs)

dbSNP: rs587781837

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130132	SCV000184965	pathogenic	Hereditary cancer-predisposing syndrome	2022-02-01	criteria provided, single submitter	clinical testing	The c.8397delT pathogenic mutation, located in coding exon 56 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 8397, causing a translational frameshift with a predicted alternate stop codon (p.Q2800Sfs*6). This alteration has been identified in 1/295 women at high risk for breast cancer who were prospectively enrolled for breast MRI surveillance (Guindalini RSC et al. Clin Cancer Res, 2019 03;25:1786-1794). 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.
GeneDx	RCV000255447	SCV000322061	pathogenic	not provided	2022-09-21	criteria provided, single submitter	clinical testing	Frameshift 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); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 28152038, 29922827, 30154229)
Genetic Services Laboratory, University of Chicago	RCV000499426	SCV000593509	pathogenic	Breast cancer, susceptibility to	2017-02-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000801010	SCV000940758	pathogenic	Ataxia-telangiectasia syndrome	2024-05-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln2800Serfs*6) 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 is present in population databases (rs587781837, gnomAD 0.003%). 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: 141556). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003460912	SCV004213939	pathogenic	Familial cancer of breast	2021-12-28	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003460912	SCV004931618	pathogenic	Familial cancer of breast	2024-02-02	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.