Submissions for variant NM_000051.4(ATM):c.2938del (p.Tyr980fs)

dbSNP: rs1565425118

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000701920	SCV000830743	pathogenic	Ataxia-telangiectasia syndrome	2023-01-05	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 578804). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr980Ilefs*12) 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).
Color Diagnostics, LLC DBA Color Health	RCV000772295	SCV000905413	pathogenic	Hereditary cancer-predisposing syndrome	2020-05-08	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 20 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics	RCV000772295	SCV002748612	pathogenic	Hereditary cancer-predisposing syndrome	2024-06-24	criteria provided, single submitter	clinical testing	The c.2938delT pathogenic mutation, located in coding exon 19 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 2938, causing a translational frameshift with a predicted alternate stop codon (p.Y980Ifs*12). 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.
Myriad Genetics, Inc.	RCV004026573	SCV004931881	pathogenic	Familial cancer of breast	2024-01-18	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.