ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.1523G>A (p.Gly508Asp) (rs1555687572)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
University of Washington Department of Laboratory Medicine,University of Washington RCV000664319 SCV000788255 likely pathogenic Juvenile polyposis syndrome 2018-05-01 criteria provided, single submitter research The SMAD4 variant designated as NM_005359.5:c.1523G>A (p.Gly508Asp) is as likely pathogenic. Testing in parents confirmed this variant be de novo in a patient with clinical history of juvenile polyposis syndrome beginning in their late teens and a negative family history for polyposis. This variant is highly conserved. It is not listed in population databases (ExAC or gnomAD). It is predicted to be damaging by in silico software programs (SIFT: “Damaging”, PolyPhen-2 “Probably Damaging”). The combined results are consistent with a classification of likely pathogenic. Bayesian analysis integrating all of this data (Tavtigian et al, 2018, PMID:29300386) gives 98% probability of pathogenicity, which is consistent with a classification of likely pathogenic. This variant is predicted to alter SMAD4 function and increase cancer risk. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study.

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