Submissions for variant NM_000051.4(ATM):c.8del (p.Leu3fs)

dbSNP: rs879254052

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235462	SCV000293310	pathogenic	not provided	2022-01-20	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 (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000554193	SCV000622872	pathogenic	Ataxia-telangiectasia syndrome	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu3Glnfs*13) 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 not present in population databases (gnomAD no frequency). 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: 246026). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV001018623	SCV001179880	pathogenic	Hereditary cancer-predisposing syndrome	2022-02-09	criteria provided, single submitter	clinical testing	The c.8delT pathogenic mutation, located in coding exon 1 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 8, causing a translational frameshift with a predicted alternate stop codon (p.L3Qfs*13). 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.
Sema4, Sema4	RCV001018623	SCV002530592	likely pathogenic	Hereditary cancer-predisposing syndrome	2021-06-14	criteria provided, single submitter	curation
Baylor Genetics	RCV003469184	SCV004211961	likely pathogenic	Familial cancer of breast	2024-02-24	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003469184	SCV004931585	pathogenic	Familial cancer of breast	2024-01-05	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.