ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5177+1G>A (rs1131691159)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000493729 SCV000581459 pathogenic Hereditary cancer-predisposing syndrome 2017-03-28 criteria provided, single submitter clinical testing Functionally-validated splicing mutation;Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Integrated Genetics/Laboratory Corporation of America RCV000587062 SCV000694298 pathogenic Ataxia-telangiectasia syndrome 2017-04-13 criteria provided, single submitter clinical testing Variant summary: The ATM c.5177+1G>A variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict loss of canonical splicing donor site. These predictions was confirmed by functional studies showing variant led to exon skipping (Soukupova_2008). This variant is absent in 125804 control chromosomes. It has been reported in AT patient as well as BrC patient. Taken together, this variant is classified as pathogenic.
Invitae RCV000587062 SCV001373174 pathogenic Ataxia-telangiectasia syndrome 2019-08-19 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 34 of the ATM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with breast cancer (PMID: 18497957). ClinVar contains an entry for this variant (Variation ID: 429076). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 18497957). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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