Submissions for variant NM_000051.4(ATM):c.1692T>A (p.Cys564Ter)

dbSNP: rs886039644

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255429	SCV000322573	likely pathogenic	not provided	2016-05-23	criteria provided, single submitter	clinical testing	This variant is denoted ATM c.1692T>A at the cDNA level and p.Cys564Ter (C564X) at the protein level. The substitution creates a nonsense variant, which changes a Cysteine to a premature stop codon (TGT>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered likely pathogenic.
Invitae	RCV001383509	SCV001582660	pathogenic	Ataxia-telangiectasia syndrome	2023-09-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 265583). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys564*) 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).
Ambry Genetics	RCV003298329	SCV004007301	pathogenic	Hereditary cancer-predisposing syndrome	2023-05-17	criteria provided, single submitter	clinical testing	The p.C564* variant (also known as c.1692T>A), located in coding exon 10 of the ATM gene, results from a T to A substitution at nucleotide position 1692. This changes the amino acid from a cysteine to a stop codon within coding exon 10. 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.
Myriad Genetics, Inc.	RCV004021035	SCV004932497	pathogenic	Familial cancer of breast	2024-01-16	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.