Submissions for variant NM_000051.4(ATM):c.2406_2407insC (p.Phe803fs)

dbSNP: rs2135421164

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002042271	SCV002109559	pathogenic	Ataxia-telangiectasia syndrome	2023-06-15	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: 1350979). 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.Phe803Leufs*12) 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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002042271	SCV003929087	likely pathogenic	Ataxia-telangiectasia syndrome	2023-04-17	criteria provided, single submitter	clinical testing	Variant summary: ATM c.2406_2407insC (p.Phe803LeufsX12) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251260 control chromosomes. To our knowledge, no occurrence of c.2406_2407insC in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics	RCV003470952	SCV004210057	likely pathogenic	Familial cancer of breast	2023-08-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV004546676	SCV005041158	pathogenic	not provided	2024-04-01	criteria provided, single submitter	clinical testing	ATM: PVS1, PM2
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV002042271	SCV005387928	pathogenic	Ataxia-telangiectasia syndrome	2024-04-18	criteria provided, single submitter	clinical testing