Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV003448568 | SCV004176057 | uncertain significance | Luscan-Lumish syndrome | 2023-06-22 | criteria provided, single submitter | clinical testing | The c.638C>G variant in SETD2 has not previously been reported in the literature and the variant is observed in 2 alleles (~0.0003% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.638C>G variant in SETD2 is located in exon 3 of this 21-exon gene and predicted to replace a moderately conserved alanine amino acid with glycine at position 213 in the kinase domain of the encoded protein. In silico predictions are not in favor of damaging effect for p.(Ala213Gly) [(CADD v1.6 = 21.3, REVEL = 0.116)]; however, there are no functional studies to support or refute these predictions. Based on available evidence this inherited c.638C>G p.(Ala213Gly) variant in SETD2 is classified as a Variant of Uncertain Significance. |