Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000212617 | SCV000170347 | benign | not specified | 2013-12-27 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Ambry Genetics | RCV000126821 | SCV000212951 | likely benign | Hereditary cancer-predisposing syndrome | 2014-09-16 | 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. |
Illumina Laboratory Services, |
RCV000323210 | SCV000430933 | uncertain significance | Lynch syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000409899 | SCV000488353 | likely benign | Lynch syndrome 1 | 2016-03-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001083829 | SCV000559194 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000212617 | SCV000601460 | benign | not specified | 2021-07-31 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000126821 | SCV000685022 | benign | Hereditary cancer-predisposing syndrome | 2015-06-11 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590738 | SCV000696238 | benign | not provided | 2016-08-15 | criteria provided, single submitter | clinical testing | Variant summary: The MSH2 c.2205C>T (p.Ile735Ile) 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. However, these predictions have yet to be confirmed by functional studies. This variant was found in 185/121382 control chromosomes (2 homozygotes), predominantly observed in the South Asian subpopulation at a frequency of 0.0109038 (180/16508). This frequency is about 19 times the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. One internal sample also carried a disease variant in BRCA1 c.3869_3870delAA, further suppporting the benign classification. Taken together, this variant is classified as benign. |
Prevention |
RCV000212617 | SCV000806027 | benign | not specified | 2017-07-06 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000212617 | SCV002760648 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV003149864 | SCV003837629 | benign | Breast and/or ovarian cancer | 2021-08-30 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000409899 | SCV004018297 | benign | Lynch syndrome 1 | 2023-03-20 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
All of Us Research Program, |
RCV000323210 | SCV004825747 | benign | Lynch syndrome | 2024-02-05 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000212617 | SCV000592543 | benign | not specified | no assertion criteria provided | clinical testing | The p.Ile735Ile variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site; in addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified in the ClinVar database, where it was classified as “benign” by GeneDX and as “likely benign” by Ambry Genetics. The variant was not identified in any of the other databases searched (dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, HGMD, COSMIC, “Mismatch Repair Genes Variant Database”, InSiGHT Colon Cancer Gene Variant Database, “Zhejiang Colon Cancer Database”, GeneInsight COGR database, and UMD). The variant was identified in an individual tested by our laboratory in a hemizygous state, with a co-occuring pathogenic MSH2 deletion of exons 12-16 in trans, increasing the likelihood that the variant does not have clinical significance. In summary, based on the above information this variant is classified as benign. | |
Mayo Clinic Laboratories, |
RCV000212617 | SCV000691910 | likely benign | not specified | no assertion criteria provided | clinical testing | ||
True Health Diagnostics | RCV000126821 | SCV000805269 | likely benign | Hereditary cancer-predisposing syndrome | 2018-05-09 | no assertion criteria provided | clinical testing |