Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002510378 | SCV002819609 | likely pathogenic | Juvenile polyposis syndrome | 2022-12-16 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the duplication of partial exon 2 in the SMAD4 gene. A presumed nomenclature of c.(-128+1_-127-1)_55dup has been designated for the purposes of this classification. It has been assumed that this is a tandem duplication in direct orientation (Richardson_GIM_2018, Newman_AJHG_2015). Although exact breakpoints of this duplication are not known, it is expected to result in a frameshift duplication change in the SMAD4 gene. The variant was absent in 21694 control chromosomes (gnomAD SVs, Structural Variants dataset). To our knowledge, no occurrence of c.(-128+1_-127-1)_55dup in individuals affected with Juvenile Polyposis Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |