Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000150424 | SCV000197604 | uncertain significance | not specified | 2013-12-27 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Gly157Glu varia nt in DNAH11 has not been previously identified in individuals with pulmonary di sease. This variant has been identified in 0.19% (7/3676) African American chrom osomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs185011953). The Glycine residue at this position is not well conserved across evolutionarily distant species, and the variant residue (Glutamic acid) h as been observed in two mammalian species (shrew and platypus). Additional compu tational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, the lack of evolutionary conservation suggests that this variant may be more likely benign, but additional information is needed to fully assess its cl inical significance. |
| Invitae | RCV000862582 | SCV001003104 | likely benign | Primary ciliary dyskinesia | 2024-01-31 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV002227077 | SCV002506252 | uncertain significance | Primary ciliary dyskinesia 7 | 2022-01-31 | criteria provided, single submitter | clinical testing | The DNAH11 c.470G>A; p.Gly157Glu variant (rs185011953), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 163093). This variant is found in the African population with an allele frequency of 0.2% (59/23,860 alleles) in the Genome Aggregation Database. The glycine at codon 157 is moderately conserved, and computational analyses predict that this variant is neutral (REVEL: 0.037). Given the lack of clinical and functional data, the significance of the p.Gly157Glu variant is uncertain at this time. |
| Gene |
RCV002281964 | SCV002571598 | uncertain significance | not provided | 2022-09-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV000862582 | SCV002635846 | likely benign | Primary ciliary dyskinesia | 2017-04-17 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |