Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV001291685 | SCV001480266 | uncertain significance | Kleefstra syndrome 2 | 2019-09-26 | criteria provided, single submitter | clinical testing | The c.7841G>T (p.Gly2614Val) variant identified in the KMT2C gene substitutes a well conserved Glycine for Valine at amino acid 2614/4912 (coding exon 38/59). This variant is found with low frequency in gnomAD (3 heterozygotes, 0 homozygotes; allele frequency: 1.19e-5) and ExAC (1 heterozygote, 0 homozygotes; allele frequency: 8.24e-6), suggesting it is not a common benign variant in the populations represented in these databases. In silico algorithms predict this variant to be Deleterious (Provean; score: -3.25) and Damaging (SIFT; score: 0.007) to the function of the canonical transcript. This variant is absent from ClinVar and does not map to a specific domain of KMT2C. To our current knowledge it has not been reported in affected individuals in the literature. Given the lack of compelling information supporting the pathogenicity of the c.7841G>T (p.Gly2614Val) variant identified in the KMT2C gene, it is reported here as a Variant of Uncertain Significance. |