rs727505321
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_001277115.2(DNAH11):c.6437G>A(p.Arg2146His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,608,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2146C) has been classified as Benign.
Frequency
Consequence
NM_001277115.2 missense
Scores
Clinical Significance
Conservation
Publications
- primary ciliary dyskinesia 7Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
- primary ciliary dyskinesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152156Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000704 AC: 17AN: 241460 AF XY: 0.0000535 show subpopulations
GnomAD4 exome AF: 0.000112 AC: 163AN: 1456376Hom.: 0 Cov.: 32 AF XY: 0.000106 AC XY: 77AN XY: 724170 show subpopulations
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74330 show subpopulations
ClinVar
Submissions by phenotype
not specified Benign:3
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p.Arg2146His in exon 38 of DNAH11: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. O f note, >10 mammals carry a histidine (His) at this position despite high nearby amino acid conservation. -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Primary ciliary dyskinesia Uncertain:1Benign:1
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The c.6437G>A (p.R2146H) alteration is located in exon 38 (coding exon 38) of the DNAH11 gene. This alteration results from a G to A substitution at nucleotide position 6437, causing the arginine (R) at amino acid position 2146 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at