rs773643407
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001369.3(DNAH5):c.8236G>T(p.Val2746Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. V2746V) has been classified as Likely benign.
Frequency
Consequence
NM_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.8236G>T | p.Val2746Leu | missense_variant | 50/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.8236G>T | p.Val2746Leu | missense_variant | 50/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.8191G>T | p.Val2731Leu | missense_variant | 50/79 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152066Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251124Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135724
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461476Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727078
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152066Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74260
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Primary ciliary dyskinesia 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Oct 02, 2020 | The inherited c.8236G>T(p.Val2746Leu) missense variant in exon 50 of 79 of DNAH5 has not been reported in affected individuals in the available literature. This variant is absent in gnomADv3indicating it is not a common benign variant in the populations represented in this database. In silico predictors suggest this variant is Neutral (Provean; score: -0.50) and Tolerated (SIFT; score: 0.3). Given the conflicting evidences regarding its pathogenicity, the c.8236G>T(p.Val2746Leu)variant identified in the DNAH5 gene is reported as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at