Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000206879 | SCV000260269 | likely pathogenic | Ataxia-telangiectasia syndrome | 2023-08-17 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change affects a donor splice site in intron 20 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with ataxia-telangiectasia and/or prostate and breast cancer (PMID: 32853339, 35220195, 35260754). ClinVar contains an entry for this variant (Variation ID: 220036). |
Ambry Genetics | RCV001018496 | SCV001179743 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-02-14 | criteria provided, single submitter | clinical testing | The c.3077+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 19 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 and will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (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. |
Color Diagnostics, |
RCV001018496 | SCV001354066 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-02-02 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the +1 position of intron 20 of the ATM gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant (also referred to as IVS20+1G>A) was found together with ATM 9064_9065insG (E3022fs) in a Turkish individual affected with ataxia-telangiectasia. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |
Ce |
RCV001531757 | SCV001747028 | likely pathogenic | not provided | 2021-03-01 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV004020519 | SCV004931664 | 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. |