Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000537231 | SCV000624008 | uncertain significance | Primary ciliary dyskinesia | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1043 of the DNAH8 protein (p.Asp1043Glu). This variant is present in population databases (rs573755164, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 454566). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Ambry Genetics | RCV002525264 | SCV003688512 | uncertain significance | Inborn genetic diseases | 2021-07-14 | criteria provided, single submitter | clinical testing | The c.3129T>A (p.D1043E) alteration is located in exon 23 (coding exon 22) of the DNAH8 gene. This alteration results from a T to A substitution at nucleotide position 3129, causing the aspartic acid (D) at amino acid position 1043 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV003144311 | SCV003831754 | uncertain significance | Spermatogenic failure 46 | 2020-06-29 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003915475 | SCV004734467 | likely benign | DNAH8-related condition | 2023-02-13 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |