rs143673459
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6
The NM_001369.3(DNAH5):c.2944C>T(p.Arg982Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R982H) has been classified as Likely benign.
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.2944C>T | p.Arg982Cys | missense_variant | 19/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.2944C>T | p.Arg982Cys | missense_variant | 19/79 | 1 | NM_001369.3 | P4 | |
ENST00000503244.2 | n.254-11561G>A | intron_variant, non_coding_transcript_variant | 4 | ||||||
DNAH5 | ENST00000681290.1 | c.2899C>T | p.Arg967Cys | missense_variant | 19/79 | A1 | |||
ENST00000637153.1 | n.214-11561G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251452Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135904
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461866Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10AN XY: 727238
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74480
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 31, 2023 | The p.R982C variant (also known as c.2944C>T), located in coding exon 19 of the DNAH5 gene, results from a C to T substitution at nucleotide position 2944. The arginine at codon 982 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at