ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.1647A>G (p.Gln549=) (rs113545983)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000587303 SCV000884551 likely benign not provided 2017-08-25 criteria provided, single submitter clinical testing The SMAD4 c.1647A>G;p.Gln549Gln variant is listed as likely benign in the ClinVar database (Variation ID: 231980). The variant is listed in the dbSNP variant database (rs113545983) with an allele frequency of 0.0154 percent (2/13004 alleles) in the Exome Variant Server and 0.002849 percent (7/245724 alleles) in the Genome Aggregation Database. The nucleotide at this position is weakly conserved across species and computational algorithms (SpliceSiteFinder-like, MaxEntScan, NNSplice, GeneSplicer, Human Splicing Finder) predict this variant will not alter splicing. One publication indicated that this variant may be associated with poor prognosis in pancreatic cancer, but is not necessarily causative for cancer (Javle 2014). Considering available information, this variant is classified as likely benign. References: Javle M et al. Biomarkers of TGF-ß signaling pathway and prognosis of pancreatic cancer. PLoS One. 2014 Jan 20;9(1):e85942.
Ambry Genetics RCV000213128 SCV000275988 likely benign Hereditary cancer-predisposing syndrome 2015-06-02 criteria provided, single submitter clinical testing
Color RCV000213128 SCV000686528 likely benign Hereditary cancer-predisposing syndrome 2016-10-09 criteria provided, single submitter clinical testing
GeneDx RCV000428814 SCV000515485 benign not specified 2015-07-31 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 RCV000587303 SCV000698572 benign not provided 2017-06-26 criteria provided, single submitter clinical testing Variant summary: The c.1647A>G (p.Gln549=) in SMAD4 gene is a synonymous change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect the normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population datasets of ExAC and gnomAD at a similar frequencies 0.000028 (3/120978 and 7/245724 chrs tested, respectively). However, the possibility of the variant to be derived from pseudogene cannot be completely ruled out. The variant has not, to our knowledge, been reported in affected individuals via published reports but is cited as Benign/Likely Benign by reputable databases/clinical laboratories. Taking together, the variant was classified as Benign.
Invitae RCV000474295 SCV000556152 likely benign Juvenile polyposis syndrome 2017-12-18 criteria provided, single submitter clinical testing
PreventionGenetics RCV000587303 SCV000806696 likely benign not provided 2017-06-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587303 SCV000889846 benign not provided 2017-11-17 criteria provided, single submitter clinical testing

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