Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
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Hunan Provincial Maternal and Child Health Care Hospital | RCV004801952 | SCV005414418 | pathogenic | Syndromic intellectual disability | no assertion criteria provided | clinical testing | Compound heterozygosity variants(NM_005481.3, c.385dup & c.932T>C) in MED16 are identified from siblings with syndromic intellectual disability. The allele frequency of the p.(Asp129GlyfsTer288) variant is 3.42×10-6, while the missense p.(Leu311Pro) variant is absent from gnomAD (Karczewski et al., 2020), and the affected residue is evolutionarily conserved (Figures 2A). Multiple in silico prediction programs (see Methods) predict that this missense change has a pathogenic effect on MED16, including a Alphamissense pathogenecity score (Cheng et al., 2023) of 0.999. No other variants in known or other genes were retained as plausible candidates in the two sisters. |