Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV001281494 | SCV001468803 | uncertain significance | Dandy-Walker syndrome; Global developmental delay | 2019-09-13 | criteria provided, single submitter | clinical testing | The inherited c.616G>C (p.Val206Leu) variant identified in the INTS1 gene substitutes a completely conserved Valine for Leucine at amino acid 206/2191 (coding exon 5/48). This variant is found with low frequency in gnomAD (1 heterozygote, 0 homozygotes; allele frequency: 4.03e-6), and is absent from ExAC, suggesting it is not a common benign variant in the populations represented in these databases. In silico algorithms do not agree on the effect of this variant, as it is predicted both Neutral (Provean; score: -1.74) and Damaging (SIFT; score: 0.019) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literauture. Given the lack of compelling evidence supporting its pathogenicity, the c.616G>C (p.Val206Leu) variant identified in the INTS1 gene is reported here as a Variant of Uncertain Significiance. |