Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000464236 | SCV000561433 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000774611 | SCV000908427 | likely benign | Hereditary cancer-predisposing syndrome | 2017-01-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192491 | SCV001360648 | benign | not specified | 2019-11-25 | criteria provided, single submitter | clinical testing | Variant summary: MSH6 c.3647-7T>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.4e-05 in 251134 control chromosomes, predominantly at a frequency of 0.00054 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in MSH6 causing Lynch Syndrome phenotype (0.00014), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.3647-7T>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign. |
All of Us Research Program, |
RCV004002154 | SCV004825475 | likely benign | Lynch syndrome | 2023-12-18 | criteria provided, single submitter | clinical testing |