Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491735 | SCV000580558 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2018-06-27 | criteria provided, single submitter | clinical testing | The c.1510+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 9 of the MSH2 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780446 | SCV000917699 | likely pathogenic | Lynch syndrome | 2018-04-30 | criteria provided, single submitter | clinical testing | Variant summary: MSH2 c.1510+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 5 splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was observed with an allele frequency of 4.1e-06 in 246122 control chromosomes (gnomAD). The variant, c.1510+1G>A, has been reported in the literature as a pathogenic/likely pathogenic variant reported by a clinical diagnostic laboratory with limited information (LaDuca_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. In 2014, one clinical diagnostic laboratory reporting the single published occurrence of this variant submitted clinical-significance assessment for this variant as "Likely Pathogenic" in ClinVar. Based on the evidence outlined above, the variant was classified as Likely Pathogenic. |
| Myriad Genetics, |
RCV003449369 | SCV004186601 | likely pathogenic | Lynch syndrome 1 | 2023-08-02 | 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. |
| Constitutional Genetics Lab, |
RCV001249922 | SCV001423939 | pathogenic | Lynch-like syndrome | 2019-07-01 | no assertion criteria provided | clinical testing |