Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825752 | SCV000967213 | likely benign | not specified | 2018-07-03 | criteria provided, single submitter | clinical testing | p.Met297Ile in exon 8 of DNAI2: This variant is classified as likely benign due to a lack of conservation across species, including mammals. Of note, more than 10 mammals have Isoleucine at this position despite high nearby amino acid conse rvation. In addition, computational prediction tools do not suggest a high likel ihood of impact to the protein. ACMG/AMP Criteria applied: BP4_Strong. |
| Ambry Genetics | RCV002372368 | SCV002687538 | likely benign | Primary ciliary dyskinesia | 2022-11-18 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV002372368 | SCV003249138 | uncertain significance | Primary ciliary dyskinesia | 2022-04-01 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 297 of the DNAI2 protein (p.Met297Ile). This variant is present in population databases (rs750750518, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DNAI2-related conditions. ClinVar contains an entry for this variant (Variation ID: 667108). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine 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. |