Submissions for variant NM_000051.4(ATM):c.6322C>T (p.Gln2108Ter)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV003585885	SCV004361792	pathogenic	Hereditary cancer-predisposing syndrome	2022-07-11	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 43 of the ATM gene, creating a 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 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003605880	SCV004428313	pathogenic	Ataxia-telangiectasia syndrome	2024-07-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln2108*) 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. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV004371484	SCV004932360	pathogenic	Familial cancer of breast	2024-01-29	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Ambry Genetics	RCV003585885	SCV005018950	pathogenic	Hereditary cancer-predisposing syndrome	2024-01-15	criteria provided, single submitter	clinical testing	The p.Q2108* pathogenic mutation (also known as c.6322C>T), located in coding exon 42 of the ATM gene, results from a C to T substitution at nucleotide position 6322. This changes the amino acid from a glutamine to a stop codon within coding exon 42. 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.