rs151287187
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001369.3(DNAH5):c.7684A>T(p.Ile2562Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000421 in 1,614,086 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic 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. I2562V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.7684A>T | p.Ile2562Phe | missense_variant | 46/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.7684A>T | p.Ile2562Phe | missense_variant | 46/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.7639A>T | p.Ile2547Phe | missense_variant | 46/79 | A1 | |||
DNAH5 | ENST00000512443.1 | n.540A>T | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000278 AC: 70AN: 251496Hom.: 0 AF XY: 0.000294 AC XY: 40AN XY: 135922
GnomAD4 exome AF: 0.000441 AC: 644AN: 1461882Hom.: 1 Cov.: 31 AF XY: 0.000418 AC XY: 304AN XY: 727242
GnomAD4 genome ? AF: 0.000237 AC: 36AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74364
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:3Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 10, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill | Jan 29, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2018 | The p.I2562F variant (also known as c.7684A>T), located in coding exon 46 of the DNAH5 gene, results from an A to T substitution at nucleotide position 7684. The isoleucine at codon 2562 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Primary ciliary dyskinesia 3 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 11, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at