ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2838+1G>T

dbSNP: rs1555083469
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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 RCV000563240 SCV000665427 likely pathogenic Hereditary cancer-predisposing syndrome 2024-01-17 criteria provided, single submitter clinical testing The c.2838+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 17 of the ATM gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000628011 SCV000748898 likely pathogenic Ataxia-telangiectasia syndrome 2023-05-31 criteria provided, single submitter clinical testing 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. This variant has not been reported in the literature in individuals affected with ATM-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 481191). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 18 of the ATM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).
Baylor Genetics RCV003459314 SCV004216245 likely pathogenic Familial cancer of breast 2021-01-27 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003459314 SCV004933270 likely pathogenic Familial cancer of breast 2024-01-18 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.

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