Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000807078 | SCV000947112 | uncertain significance | Primary ciliary dyskinesia | 2018-10-18 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not available"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DNAH8-related disease. This variant is present in population databases (rs770020515, ExAC 0.003%). This sequence change replaces glycine with glutamic acid at codon 70 of the DNAH8 protein (p.Gly70Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. |
Ambry Genetics | RCV002537242 | SCV003612797 | uncertain significance | Inborn genetic diseases | 2022-11-18 | criteria provided, single submitter | clinical testing | The c.209G>A (p.G70E) alteration is located in exon 2 (coding exon 1) of the DNAH8 gene. This alteration results from a G to A substitution at nucleotide position 209, causing the glycine (G) at amino acid position 70 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003413620 | SCV004106451 | uncertain significance | DNAH8-related condition | 2023-04-19 | criteria provided, single submitter | clinical testing | The DNAH8 c.209G>A variant is predicted to result in the amino acid substitution p.Gly70Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-38690794-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |