Submissions for variant NM_000051.4(ATM):c.709dup (p.Thr237fs)

dbSNP: rs2079758064

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001036994	SCV001200385	pathogenic	Ataxia-telangiectasia syndrome	2023-08-07	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with ATM-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 835979). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr237Asnfs*17) 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	RCV001183124	SCV001348779	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 7 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. 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.
GeneDx	RCV001549886	SCV001770119	pathogenic	not provided	2021-06-30	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 (Lek 2016); Observed in individuals with aggressive prostate cancer in published literature (Nguyen-Dumont 2020); This variant is associated with the following publications: (PMID: 32338768, 33436325, 27535533)
Ambry Genetics	RCV001183124	SCV002663099	pathogenic	Hereditary cancer-predisposing syndrome	2023-04-05	criteria provided, single submitter	clinical testing	The c.709dupA pathogenic mutation, located in coding exon 6 of the ATM gene, results from a duplication of A at nucleotide position 709, causing a translational frameshift with a predicted alternate stop codon (p.T237Nfs*17). 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.