ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.1473T>C (p.Gly491=) (rs1207826883)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000583643 SCV000691402 likely benign Hereditary cancer-predisposing syndrome 2017-10-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780718 SCV000918226 uncertain significance not specified 2018-01-22 criteria provided, single submitter clinical testing Variant summary: The SMAD4 c.1473T>C (p.Gly491Gly) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Though one in silico tool predicts a damaging outcome for this variant, 5/5 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 1/246214 control chromosomes at a frequency of 0.0000041, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic SMAD4 variant (0.000002), however due to pseudogene interference these data may not be relied upon. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign.

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