Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
All of Us Research Program, |
RCV004003521 | SCV004834336 | uncertain significance | Lynch syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This variant causes a G to C nucleotide substitution at the -13 position in the 5' untranslated region of the PMS2 gene. To our knowledge, functional studies have not been reported for this variant. Splice site prediction tools suggest that this variant may not impact RNA splicing. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has been identified in 3/249854 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Department of Pathology and Laboratory Medicine, |
RCV000503818 | SCV000592913 | uncertain significance | Endometrial carcinoma | no assertion criteria provided | clinical testing | The p.? (c.-13G>C) variant in exon 1 of the PMS2 gene has not been reported in the literature nor previously identified by our laboratory. This variant did not show up in the databases (dbSNP, NHLBI Exome sequencing project (exome variant server), HGMD, LOVD, COSMIC, UMD, ClinVar, or BIC) and it is unknown if it may or may not be causative of the disorder. It is unlikely that this will cause a missense mutation as it occurs outside of the translated sequence. This residue has not been seen in mammals and computational analyses (PolyPhen2, SIFT, AlignGVGD) and it is unknown if this suggests a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant cannot be determined with certainty at this time; however based upon the arguments described above, we find this variant to be a VARIANT OF UNKNOWN SIGNIFICANCE. |