Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220376 | SCV000273654 | likely benign | Hereditary cancer-predisposing syndrome | 2017-07-31 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV000630356 | SCV000751312 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-05-28 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003997813 | SCV004822114 | uncertain significance | Lynch syndrome | 2023-09-09 | criteria provided, single submitter | clinical testing | This variant causes a C to A nucleotide substitution at the -4 position of intron 2 of the PMS2 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified 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, |
RCV001358033 | SCV001553670 | uncertain significance | Carcinoma of colon | no assertion criteria provided | clinical testing | The PMS2 c.164-4C>A variant was not identified in the literature. The variant was identified in dbSNP (rs876658444) as “with likely benign allele” and ClinVar (classified as likely benign by Ambry Genetics and Invitae). The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The c.164-4C>A variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions nor does it affect positions -3 and -5 to -12, which are also part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |