rs114220185
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001369.3(DNAH5):c.88C>T(p.Arg30Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,614,086 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R30R) 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.88C>T | p.Arg30Trp | missense_variant | 2/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.88C>T | p.Arg30Trp | missense_variant | 2/79 | 1 | NM_001369.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00129 AC: 196AN: 152176Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.000502 AC: 126AN: 251220Hom.: 1 AF XY: 0.000457 AC XY: 62AN XY: 135750
GnomAD4 exome AF: 0.000236 AC: 345AN: 1461792Hom.: 2 Cov.: 40 AF XY: 0.000226 AC XY: 164AN XY: 727202
GnomAD4 genome ? AF: 0.00129 AC: 197AN: 152294Hom.: 2 Cov.: 33 AF XY: 0.00130 AC XY: 97AN XY: 74476
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 23, 2020 | 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. - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Primary ciliary dyskinesia 3 Uncertain:2
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 17, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at