rs189432084
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001277115.2(DNAH11):āc.5132A>Gā(p.Gln1711Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,600,310 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001277115.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.5132A>G | p.Gln1711Arg | missense_variant | 30/82 | 5 | NM_001277115.2 | ENSP00000475939.1 |
Frequencies
GnomAD3 genomes AF: 0.000322 AC: 49AN: 152120Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000531 AC: 121AN: 228082Hom.: 0 AF XY: 0.000577 AC XY: 71AN XY: 122958
GnomAD4 exome AF: 0.000462 AC: 669AN: 1448072Hom.: 3 Cov.: 31 AF XY: 0.000481 AC XY: 346AN XY: 718790
GnomAD4 genome AF: 0.000322 AC: 49AN: 152238Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20AN XY: 74440
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 12, 2015 | This alteration is classified as 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
DNAH11-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 04, 2023 | The DNAH11 c.5132A>G variant is predicted to result in the amino acid substitution p.Gln1711Arg. This variant has been reported along with additional DNAH11 variants in individuals with primary ciliary dyskinesia (Table 4, Sherman et al. 2020. PubMed ID: 32662935; Alsamri et al. 2021. PubMed ID: 34768622). This variant is reported in 0.081% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 03, 2017 | p.Gln1711Arg in exon 30 of DNAH11: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. O f note, shrew, tenrec, and platypus have an arginine (Arg) at this position desp ite high nearby amino acid conservation. In addition, computational prediction t ools do not suggest a high likelihood of impact to the protein. It has also been identified in 0.2% (48/26256) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs189432084). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at