ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.1653A>G (p.Leu551=) (rs199526820)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162721 SCV000213183 likely benign Hereditary cancer-predisposing syndrome 2014-10-24 criteria provided, single submitter clinical testing
Color RCV000162721 SCV000686529 likely benign Hereditary cancer-predisposing syndrome 2016-11-22 criteria provided, single submitter clinical testing
Counsyl RCV000123261 SCV000489064 likely benign Juvenile polyposis syndrome 2016-08-10 criteria provided, single submitter clinical testing
GeneDx RCV000439984 SCV000514710 benign not specified 2015-04-30 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.
Integrated Genetics/Laboratory Corporation of America RCV000439984 SCV000920224 benign not specified 2017-10-26 criteria provided, single submitter clinical testing Variant summary: The SMAD4 c.1653A>G (p.Leu551Leu) 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. 3/5 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 13/276566 control chromosomes (gnomAD) at a frequency of 0.000047, which is approximately 24 times the estimated maximal expected allele frequency of a pathogenic SMAD4 variant (0.000002), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Invitae RCV000123261 SCV000166568 likely benign Juvenile polyposis syndrome 2017-11-07 criteria provided, single submitter clinical testing

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