Submissions for variant NM_000051.4(ATM):c.7880del (p.Tyr2627fs)

dbSNP: rs1057516599

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000409111	SCV000485929	likely pathogenic	Ataxia-telangiectasia syndrome	2016-03-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000657502	SCV000779237	pathogenic	not provided	2019-09-16	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 a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29922827)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000409111	SCV000937541	pathogenic	Ataxia-telangiectasia syndrome	2024-12-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr2627Leufs*4) 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 (no rsID available, 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: 370576). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV001026909	SCV001189383	pathogenic	Hereditary cancer-predisposing syndrome	2024-06-03	criteria provided, single submitter	clinical testing	The c.7880delA pathogenic mutation, located in coding exon 52 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 7880, causing a translational frameshift with a predicted alternate stop codon (p.Y2627Lfs*4). 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.
Color Diagnostics, LLC DBA Color Health	RCV001026909	SCV001340191	pathogenic	Hereditary cancer-predisposing syndrome	2019-11-04	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 53 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. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250804 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Baylor Genetics	RCV003470327	SCV004210093	likely pathogenic	Familial cancer of breast	2023-08-02	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003470327	SCV004933857	pathogenic	Familial cancer of breast	2024-02-01	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000657502	SCV005623125	likely pathogenic	not provided	2024-07-05	criteria provided, single submitter	clinical testing	The ATM c.7880del (p.Tyr2627Leufs*4) variant alters the translational reading frame of the ATM mRNA and is predicted to cause the premature termination of ATM protein synthesis. This variant has been has not been reported in individuals with ATM-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/250804 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as likely pathogenic.