ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.478_482del (p.Ser160fs) (rs587780624)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122852 SCV000166110 pathogenic Ataxia-telangiectasia syndrome 2020-10-20 criteria provided, single submitter clinical testing This sequence change deletes 5 nucleotides from exon 5 of the ATM mRNA (c.478_482delTCTCA), causing a frameshift at codon 160. This creates a premature translational stop signal (p.Ser160Alafs*23) and is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individual(s) with personal and/or family history of breast and/or ovarian cancer (PMID: 26270727). ClinVar contains an entry for this variant (Variation ID: 185501). Loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000164941 SCV000215630 pathogenic Hereditary cancer-predisposing syndrome 2018-05-31 criteria provided, single submitter clinical testing The c.478_482delTCTCA pathogenic mutation, located in coding exon 4 of the ATM gene, results from a deletion of 5 nucleotides at nucleotide positions 478 to 482, causing a translational frameshift with a predicted alternate stop codon (p.S160Afs*23). This alteration was reported in an individual with ataxia telangiectasia. The second ATM alteration was not identified for this patient, but protein analysis showed severely reduced protein levels (Izatt L et al. Eur. J. Hum. Genet. 1999 Apr;7:310-20). 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 RCV000484842 SCV000564607 pathogenic not provided 2019-07-19 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); Reported in the compound heterozygous state in a child with ataxia-telangiectasia (Bakhtiar 2018); This variant is associated with the following publications: (PMID: 31447099, 31360874, 30420857, 10234507, 26270727, 21933854)
Counsyl RCV000122852 SCV000678112 likely pathogenic Ataxia-telangiectasia syndrome 2015-05-12 criteria provided, single submitter clinical testing
Color Health, Inc RCV000164941 SCV000682221 pathogenic Hereditary cancer-predisposing syndrome 2020-04-06 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000484842 SCV001446937 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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