Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000220104 | SCV000273116 | likely benign | Hereditary cancer-predisposing syndrome | 2023-08-04 | 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. |
Prevention |
RCV000679293 | SCV000806004 | uncertain significance | not provided | 2017-09-01 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000220104 | SCV000904835 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-20 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 54 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with endometrial cancer (PMID: 27443514), and has been observed in 1/60466 cases, 0/53461 unaffected controls in a large breast cancer case-control study (PMID: 33471991). 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. |
Invitae | RCV000814579 | SCV000954992 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 54 of the MSH2 protein (p.Ala54Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 229782). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. 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. |
Sema4, |
RCV000220104 | SCV002534383 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-05 | criteria provided, single submitter | curation | |
All of Us Research Program, |
RCV003997771 | SCV004831894 | uncertain significance | Lynch syndrome | 2023-01-10 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 54 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with endometrial cancer (PMID: 27443514), and has been observed in 1/60466 cases, 0/53461 unaffected controls in a large breast cancer case-control study (PMID: 33471991). 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. |