Submissions for variant NM_000051.4(ATM):c.8292_8293del (p.Ser2764fs)

dbSNP: rs879254036

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236646	SCV000293246	pathogenic	not provided	2023-06-09	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; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals with breast cancer or Ewing sarcoma (Guindalini et al., 2022; Morfouace et al., 2023); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36470093, 34887416, 29922827, 35264596)
Invitae	RCV000477401	SCV000547148	pathogenic	Ataxia-telangiectasia syndrome	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser2764Argfs*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 0.002%). 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: 245989). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000566679	SCV000665273	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-26	criteria provided, single submitter	clinical testing	The c.8292_8293delTG pathogenic mutation, located in coding exon 56 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 8292 to 8293, causing a translational frameshift with a predicted alternate stop codon (p.S2764Rfs*4). 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.
Mendelics	RCV000477401	SCV000838613	pathogenic	Ataxia-telangiectasia syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000566679	SCV001347692	pathogenic	Hereditary cancer-predisposing syndrome	2021-02-17	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 57 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 been identified in 2/282764 chromosomes 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.
Sema4, Sema4	RCV000566679	SCV002527241	likely pathogenic	Hereditary cancer-predisposing syndrome	2021-11-10	criteria provided, single submitter	curation
Baylor Genetics	RCV003475838	SCV004203738	likely pathogenic	Familial cancer of breast	2023-10-30	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003475838	SCV004931112	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.