ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4236+1G>T (rs876660674)

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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 RCV000220335 SCV000278294 likely pathogenic Hereditary cancer-predisposing syndrome 2019-04-14 criteria provided, single submitter clinical testing The c.4236+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 27 of the ATM gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Invitae RCV000628077 SCV000748967 likely pathogenic Ataxia-telangiectasia syndrome 2017-11-24 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 28 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 not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 233837). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Counsyl RCV000628077 SCV000800098 likely pathogenic Ataxia-telangiectasia syndrome 2018-05-22 criteria provided, single submitter clinical testing
Color Health, Inc RCV000220335 SCV000904839 likely pathogenic Hereditary cancer-predisposing syndrome 2020-04-23 criteria provided, single submitter clinical testing

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