ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1607+1G>T (rs772926890)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000203930 SCV000261188 pathogenic Ataxia-telangiectasia syndrome 2019-02-14 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 10 of the ATM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs772926890, ExAC 0.002%). This variant has been observed to be homozygous or in combination with another ATM pathogenic variant in several individuals affected with ataxia telangiectasia (PMID: 9450906, 17124347, 10330348, 9443866, 23454770). This variant is also known as IVS12+1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 220555). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 9450906, 9443866, 23454770, 10330348). 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.
GeneDx RCV000235749 SCV000293070 pathogenic not provided 2017-11-29 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.1607+1G>T or IVS10+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 10 of the ATM gene. The variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant, previously reported as IVS12+1G>T using alternate exon numbering, has been reported in both the homozygous state and compound heterozygous state in multiple individuals with Ataxia-telangiectasia (Gilad 1998, Telatar 1998, Magliozzi 2006, Chessa 2009). Based on current evidence, we consider ATM c.1607+1G>T to be pathogenic.
Counsyl RCV000203930 SCV000485314 likely pathogenic Ataxia-telangiectasia syndrome 2015-11-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563715 SCV000667940 pathogenic Hereditary cancer-predisposing syndrome 2019-07-18 criteria provided, single submitter clinical testing Functionally-validated splicing mutation ;Detected in individual(s) satisfying established diagnostic criteria for classic disease in trans with a mutation or mutation is homozygous;Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Deficient protein function in appropriate functional assay(s)
Color RCV000563715 SCV001351463 pathogenic Hereditary cancer-predisposing syndrome 2020-02-05 criteria provided, single submitter clinical testing

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