Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001079120 | SCV000260116 | benign | Hereditary nonpolyposis colorectal neoplasms | 2023-10-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000562101 | SCV000662253 | likely benign | Hereditary cancer-predisposing syndrome | 2016-06-28 | 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. |
| Color Diagnostics, |
RCV000562101 | SCV000685027 | likely benign | Hereditary cancer-predisposing syndrome | 2017-02-13 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587617 | SCV000696242 | likely benign | not provided | 2017-03-30 | criteria provided, single submitter | clinical testing | Variant summary: The MSH2 c.2248T>C (p.Leu750Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not significantly affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 6 of 121332 control chromosomes, predominantly observed in the South Asian subpopulation at a frequency of 0.000303 (5/16500). This frequency is nearly equivalent to the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683), suggesting this is may be a benign polymorphism found primarily in the populations of South Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely benign. |
| All of Us Research Program, |
RCV003997594 | SCV004825792 | likely benign | Lynch syndrome | 2023-10-06 | criteria provided, single submitter | clinical testing |