ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.852A>G (p.Gln284=) (rs144378484)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000617127 SCV000212827 likely benign Cardiovascular phenotype 2014-11-28 criteria provided, single submitter clinical testing
Invitae RCV000200571 SCV000254846 likely benign Juvenile polyposis syndrome 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000200571 SCV000488072 likely benign Juvenile polyposis syndrome 2015-12-23 criteria provided, single submitter clinical testing
GeneDx RCV000417748 SCV000514708 benign not specified 2015-05-05 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.
Color RCV000162465 SCV000691440 likely benign Hereditary cancer-predisposing syndrome 2016-06-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589728 SCV000698582 likely benign not provided 2016-10-06 criteria provided, single submitter clinical testing Variant summary: The SMAD4 c.852A>G (p.Gln284Gln) variant causes a synonymous change involving a conserved nucleotide with 4/5 splice prediction tools predicting an impact on splicing and ESE finder predicts that this variant may affect ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 5/121408 (1/24283), predominantly in the European (Non-Finnish) cohort, 5/66740 (1/13347), which does exceed the estimated maximal expected allele frequency for a pathogenic SMAD4 variant of 1/500000. Therefore, suggesting the variant could be a common polymorphism found in population(s) of European (Non-Finnish) origin, however, this observation needs to be cautiously considered due to presence of a pseudogene possibly being captured. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. However, clinical diagnostic laboratories have cited the variant with conflicting classifications "likely benign" or "uncertain significance." Therefore, the variant of interest has been classified as "Likely Benign," until additional information becomes available (ie, clinical and/or functional studies).
Illumina Clinical Services Laboratory,Illumina RCV001124423 SCV001283378 likely benign Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 2017-04-28 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 Clinical Services Laboratory,Illumina RCV001124424 SCV001283379 likely benign Myhre syndrome 2017-04-28 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 Clinical Services Laboratory,Illumina RCV000200571 SCV001283380 likely benign Juvenile polyposis syndrome 2017-04-28 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.

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