Total submissions: 29
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000034710 | SCV000149791 | likely benign | not provided | 2021-10-27 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 25637381, 23399955, 25742471, 26919633, 21835029, 27153395, 30719162, 25695693, 25314059, 25318351, 22703879, 25980754, 25356985, 25589618, 27443514, 28196074, 28451460) |
Invitae | RCV001420980 | SCV000166566 | benign | Juvenile polyposis syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002310997 | SCV000187245 | benign | Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome | 2018-11-06 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Illumina Laboratory Services, |
RCV000383039 | SCV000409102 | likely benign | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Illumina Laboratory Services, |
RCV000123259 | SCV000409103 | likely benign | Generalized juvenile polyposis/juvenile polyposis coli | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Illumina Laboratory Services, |
RCV000327173 | SCV000409104 | likely benign | Myhre syndrome | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
ARUP Laboratories, |
RCV000034710 | SCV000605222 | likely benign | not provided | 2022-04-04 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000123259 | SCV000784868 | uncertain significance | Generalized juvenile polyposis/juvenile polyposis coli | 2017-01-18 | criteria provided, single submitter | clinical testing | |
Preventiongenetics, |
RCV000034710 | SCV000806695 | likely benign | not provided | 2017-08-18 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000034710 | SCV000889845 | likely benign | not provided | 2023-05-10 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000771070 | SCV000902594 | benign | Hereditary cancer-predisposing syndrome | 2016-03-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000213006 | SCV000918227 | benign | not specified | 2021-02-08 | criteria provided, single submitter | clinical testing | Variant summary: SMAD4 c.1573A>G (p.Ile525Val) results in a conservative amino acid change located in the SMAD domain, Dwarfin-type (IPR001132) of 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 0.00059 in 254026 control chromosomes, predominantly at a frequency of 0.00098 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 490 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 Latino origin. c.1573A>G has been reported in the literature in both non-cancer controls (example, Johnston_2012, Tram_2011) as well as in 2 patients with gastrointestinal polyposis (example, Ngeow_2013) and in others with cancer phenotypes and phenotypes not specified (example, Yorczyk_2015, Yurgelun_2015, Ring_2016, Maxwell_2016, Pelusi_2019, Tung_2015). The variant was also reported in somatic cancer tissues (example, Li_2015, Siroy_2015, Hamblin_2017). These report(s) do 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. 14 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. The predominant consensus among all submitters is benign/likely benign (n=13). Based on the evidence outlined above and in alignment with the predominant consensus, the variant was classified as benign. |
Mendelics | RCV000123259 | SCV001140895 | benign | Generalized juvenile polyposis/juvenile polyposis coli | 2019-05-28 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV001170612 | SCV001333201 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2021-01-15 | criteria provided, single submitter | clinical testing | |
NIHR Bioresource Rare Diseases, |
RCV000383039 | SCV001439414 | likely benign | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2018-01-01 | criteria provided, single submitter | research | BS1 +BP2 |
Genetic Services Laboratory, |
RCV000213006 | SCV002067453 | likely benign | not specified | 2020-11-23 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000771070 | SCV002538308 | benign | Hereditary cancer-predisposing syndrome | 2020-11-28 | criteria provided, single submitter | curation | |
Ce |
RCV000034710 | SCV002585684 | benign | not provided | 2022-08-01 | criteria provided, single submitter | clinical testing | SMAD4: PP2, BS1, BS2 |
Myriad Genetics, |
RCV000383039 | SCV004017788 | 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. |
Center for Genomic Medicine, |
RCV000213006 | SCV004026943 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034710 | SCV000043501 | variant of unknown significance | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Uncertain significance. |
CSER _CC_NCGL, |
RCV000148889 | SCV000190634 | likely benign | Gastrointestinal polyposis | 2014-06-01 | no assertion criteria provided | research | |
University of Washington Department of Laboratory Medicine, |
RCV000383039 | SCV001446374 | benign | Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome | 2019-05-24 | no assertion criteria provided | research | |
Genome Diagnostics Laboratory, |
RCV000034710 | SCV001808810 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000034710 | SCV001919862 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000034710 | SCV001930102 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000034710 | SCV001951781 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000034710 | SCV001964560 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000034710 | SCV002035606 | likely benign | not provided | no assertion criteria provided | clinical testing |