Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169058 | SCV000220220 | likely pathogenic | Ataxia-telangiectasia syndrome | 2014-04-03 | criteria provided, single submitter | literature only | |
Ambry Genetics | RCV000570113 | SCV000665591 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-13 | criteria provided, single submitter | clinical testing | The c.7927+5delG intronic variant, located in intron 52 of the ATM gene, results from a deletion of one nucleotide within intron 52 of the ATM gene. This variant has been reported in individual(s) with ataxia-telangiectasia and designated as IVS55+5delG and 7789del139 (Cavaciuti E et al. Genes Chromosomes Cancer, 2005 Jan;42:1-9). 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). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV000169058 | SCV000748854 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-08-03 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 53 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with ataxia-telangiectasia (PMID: 15390180). This variant is also known as IVS55 _x0005_+5 delG. ClinVar contains an entry for this variant (Variation ID: 188745). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV004700521 | SCV005201685 | likely pathogenic | not provided | 2023-12-28 | criteria provided, single submitter | clinical testing | Intronic +5 splice site variant in a gene for which loss-of-function is a known mechanism of disease, and splice predictors support a deleterious effect; Observed in association with ataxia telangiectasia (PMID: 15390180); Not observed at significant frequency in large population cohorts (gnomAD); Also known as IVS55+5delG; This variant is associated with the following publications: (PMID: 31691010, 27535533, 15390180) |