rs35900306
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001369.3(DNAH5):c.7274G>A(p.Arg2425His) variant causes a missense change. The variant allele was found at a frequency of 0.0044 in 1,614,062 control chromosomes in the GnomAD database, including 210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2425C) has been classified as Likely benign.
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.7274G>A | p.Arg2425His | missense_variant | 44/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.7274G>A | p.Arg2425His | missense_variant | 44/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.7229G>A | p.Arg2410His | missense_variant | 44/79 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0215 AC: 3276AN: 152088Hom.: 98 Cov.: 32
GnomAD3 exomes AF: 0.00642 AC: 1613AN: 251414Hom.: 47 AF XY: 0.00500 AC XY: 680AN XY: 135886
GnomAD4 exome AF: 0.00261 AC: 3815AN: 1461856Hom.: 111 Cov.: 32 AF XY: 0.00228 AC XY: 1656AN XY: 727228
GnomAD4 genome AF: 0.0216 AC: 3282AN: 152206Hom.: 99 Cov.: 32 AF XY: 0.0207 AC XY: 1543AN XY: 74416
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:3
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 24, 2014 | This alteration is classified as 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. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Arg2425His in exon 44 of DNAH5: This variant is not expected to have clinical si gnificance because it has been identified in 7.3% (322/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs35900306). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 31, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Primary ciliary dyskinesia 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 21, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at