Submissions for variant NM_000051.4(ATM):c.6814delinsCA (p.Glu2272fs)

dbSNP: rs1565520117

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000702385	SCV000831237	pathogenic	Ataxia-telangiectasia syndrome	2023-05-11	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ATM-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change creates a premature translational stop signal (p.Glu2272Glnfs*8) 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).
Ambry Genetics	RCV002360807	SCV002664923	pathogenic	Hereditary cancer-predisposing syndrome	2023-07-28	criteria provided, single submitter	clinical testing	The c.6814delGinsCA pathogenic mutation, located in coding exon 46 of the ATM gene, results from the deletion of one nucleotide and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon (p.E2272Qfs*8). 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.
PreventionGenetics, part of Exact Sciences	RCV004547870	SCV004114554	pathogenic	ATM-related disorder	2022-11-21	criteria provided, single submitter	clinical testing	The ATM c.6814delinsCA variant is predicted to result in a frameshift and premature protein termination (p.Glu2272Glnfs*8). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in ATM are expected to be pathogenic. It is interpreted as pathogenic in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/579169/). This variant is interpreted as pathogenic.
Baylor Genetics	RCV003460977	SCV004213967	likely pathogenic	Familial cancer of breast	2021-10-20	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003460977	SCV004932700	pathogenic	Familial cancer of breast	2024-01-30	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.