Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002310678 | SCV000172948 | likely benign | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2018-12-31 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Invitae | RCV001450076 | SCV000253438 | likely benign | Juvenile polyposis syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000586799 | SCV000566288 | likely benign | not provided | 2021-03-23 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 24728327, 25980754, 22843233) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000122058 | SCV000602200 | uncertain significance | not specified | 2017-04-10 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000129038 | SCV000686562 | likely benign | Hereditary cancer-predisposing syndrome | 2020-03-21 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000122058 | SCV000698583 | benign | not specified | 2019-05-24 | criteria provided, single submitter | clinical testing | Variant summary: SMAD4 c.880A>G (p.Met294Val) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 282090 control chromosomes, predominantly at a frequency of 0.0016 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 800 fold of the estimated maximal expected allele frequency for a pathogenic variant in SMAD4 causing Juvenile Polyposis Syndrome phenotype (2e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. The variant, c.880A>G, was reported in one patient who underwent genetics testing for Lynch syndrome, however without strong evidence for pathogenicity (Yurgelun_2015). The report does not provide unequivocal conclusions about association of the variant with Juvenile Polyposis Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant three times as likely benign and three times as uncertain significance. Based on the evidence outlined above, the variant was classified as benign. |
Counsyl | RCV000195767 | SCV000786418 | likely benign | Generalized juvenile polyposis/juvenile polyposis coli | 2018-04-27 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000586799 | SCV002009678 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000129038 | SCV002538355 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-11 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV003315778 | SCV004017800 | likely benign | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2023-04-10 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. Homozygosity has been confirmed in one or more individuals. As homozygosity for pathogenic variants in this gene is generally assumed to result in embryonic lethality, this variant is unlikely to be pathogenic. |
Prevention |
RCV003925209 | SCV004751667 | likely benign | SMAD4-related condition | 2021-02-03 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
ITMI | RCV000122058 | SCV000086269 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Genetic Services Laboratory, |
RCV000122058 | SCV003840069 | likely benign | not specified | 2022-05-12 | no assertion criteria provided | clinical testing |