Submissions for variant NM_000051.4(ATM):c.6529C>T (p.Gln2177Ter)

dbSNP: rs766706861

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001868392	SCV002228896	pathogenic	Ataxia-telangiectasia syndrome	2021-04-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln2177*) 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). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with breast cancer (PMID: 28724667). This variant is present in population databases (rs766706861, ExAC no frequency).
Baylor Genetics	RCV003470879	SCV004212127	likely pathogenic	Familial cancer of breast	2023-01-04	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003470879	SCV004933309	pathogenic	Familial cancer of breast	2024-01-30	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	RCV004039956	SCV005018989	pathogenic	Hereditary cancer-predisposing syndrome	2023-09-20	criteria provided, single submitter	clinical testing	The p.Q2177* pathogenic mutation (also known as c.6529C>T), located in coding exon 44 of the ATM gene, results from a C to T substitution at nucleotide position 6529. This changes the amino acid from a glutamine to a stop codon within coding exon 44. This alteration has been reported in breast cancer cohorts (Yang Z et al. Breast Cancer Res Treat, 2019 Apr;174:639-647; Paixão D et al. Front Oncol, 2022 Aug;12:976959). This alteration has also been reported in conjunction with a second truncating variant in a patient with ataxia telangiectasia (Kim J et al. Nature, 2023 Jul;619:828-836). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702268	SCV001928393	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001702268	SCV001967267	pathogenic	not provided		no assertion criteria provided	clinical testing