Submissions for variant NM_000051.4(ATM):c.8432dup (p.Ser2812fs)

dbSNP: rs587782558

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166814	SCV000217628	pathogenic	Hereditary cancer-predisposing syndrome	2024-08-01	criteria provided, single submitter	clinical testing	The c.8432dupA pathogenic mutation, located in coding exon 57 of the ATM gene, results from a duplication of A at nucleotide position 8432, causing a translational frameshift with a predicted alternate stop codon (p.S2812Vfs*3). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001051125	SCV001215263	pathogenic	Ataxia-telangiectasia syndrome	2024-12-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser2812Valfs*3) 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: 187124). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000166814	SCV001356069	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 58 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.
Myriad Genetics, Inc.	RCV004019990	SCV004932270	pathogenic	Familial cancer of breast	2024-02-02	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
GeneDx	RCV001689710	SCV005332338	likely pathogenic	not provided	2021-10-22	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); Observed in individuals with colorectal cancer (PMID: 33294277); This variant is associated with the following publications: (PMID: 33294277)
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001689710	SCV001906179	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001689710	SCV001975831	pathogenic	not provided		no assertion criteria provided	clinical testing