ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.717_720del (p.Phe239fs)

dbSNP: rs587782660
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132076 SCV000187140 pathogenic Hereditary cancer-predisposing syndrome 2023-02-28 criteria provided, single submitter clinical testing The c.717_720delCCTC pathogenic mutation, located in coding exon 6 of the ATM gene, results from a deletion of 4 nucleotides at nucleotide positions 717 to 720, causing a translational frameshift with a predicted alternate stop codon (p.F239Lfs*15). This alteration has been reported in numerous individuals with ataxia-telangiectasia (Cavalieri S et al. Hum. Mutat. 2006 Oct;27:1061; Magliozzi M et al. Dis. Markers 2006;22:257-64; Verhagen MM et al. Neurology 2009 Aug;73:430-7). Haplotype analyses have suggested a possible Sicilian founder effect (Chessa L et al. Ann. Hum. Genet. 2009 Sep;73:532-9). 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.
GeneDx RCV000484835 SCV000568311 pathogenic not provided 2018-08-13 criteria provided, single submitter clinical testing This deletion of 4 nucleotides in ATM is denoted c.717_720delCCTC at the cDNA level and p.Phe239LeufsX15 (F239LfsX15) at the protein level. The normal sequence, with the bases that are deleted in braces, is TCTT[CCTC]AAGA. The deletion causes a frameshift which changes a Phenylalanine to a Leucine at codon 239, and creates a premature stop codon at position 15 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM c.717_720delCCTC has been observed in both the compound heterozygous and homozygous states in individuals with Ataxia-telangiectasia (Cavalieri 2006, Magliozzi 2006, Verhagen 2009). We consider this variant to be pathogenic.
Invitae RCV000798600 SCV000938223 pathogenic Ataxia-telangiectasia syndrome 2023-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe239Leufs*15) 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 premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 16941484, 17124347, 19691550, 22213089, 23454770). This variant is also known as 717delCCTC. ClinVar contains an entry for this variant (Variation ID: 142709). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV004019746 SCV004931560 pathogenic Familial cancer of breast 2024-01-10 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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