Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001256637 | SCV001430673 | likely pathogenic | Microcephaly 20, primary, autosomal recessive | 2020-08-21 | criteria provided, single submitter | clinical testing | The KIF14 variant c.14G>T (p.(Ser5Ile)) is not found in known databases (ExAC or gnomAD), it affects a weakly conserved amino acid and there is a large physicochemical difference between Ser and Ile. In our institute the variant was found in homozygous state in two affected brothers matching the phonotype of primary, autosomal recessive microcephaly type 20. The parents were consanguineous and heterozygous carriers of this variant. Thus, we consider this variant to be likely pathogenic. ACMG criteria used for classification: PM2, PP4, PP1_strong. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001553587 | SCV001774491 | uncertain significance | not specified | 2021-07-20 | criteria provided, single submitter | clinical testing | Variant summary: KIF14 c.14G>T (p.Ser5Ile) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 244936 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.14G>T in individuals affected with Joubert Syndrome And Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic for primary autosomal recessive Microcephaly type 20 citing internal data on its presence in two homozygous affected brothers from a single family. Based on the evidence outlined above, until additional clinical and functional studies are reported, the variant was classified as uncertain significance. |