Submissions for variant NM_000051.4(ATM):c.192del (p.Leu64fs)

dbSNP: rs878853490

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231922	SCV000282885	pathogenic	Ataxia-telangiectasia syndrome	2023-09-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu64Phefs*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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 236681). 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).
Counsyl	RCV000231922	SCV000486595	likely pathogenic	Ataxia-telangiectasia syndrome	2016-06-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000231922	SCV000918565	likely pathogenic	Ataxia-telangiectasia syndrome	2018-09-28	criteria provided, single submitter	clinical testing	Variant summary: ATM c.192delA (p.Leu64PhefsX12) 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 (eg. p.Glu73fsX26, p.Tyr171X, p.Tyr264fsX12). The variant was absent in 273852 control chromosomes. To our knowledge, no occurrence of c.192delA in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Ambry Genetics	RCV001013747	SCV001174370	pathogenic	Hereditary cancer-predisposing syndrome	2023-01-03	criteria provided, single submitter	clinical testing	The c.192delA pathogenic mutation, located in coding exon 3 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 192, causing a translational frameshift with a predicted alternate stop codon (p.L64Ffs*12). 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.
Baylor Genetics	RCV003469122	SCV004212104	likely pathogenic	Familial cancer of breast	2023-01-24	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003469122	SCV004931661	pathogenic	Familial cancer of breast	2024-01-09	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.