chr5-13794031-G-GT
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001369.3(DNAH5):c.7914_7915insA(p.Arg2639ThrfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. K2638K) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001369.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.7914_7915insA | p.Arg2639ThrfsTer19 | frameshift_variant | 48/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.7914_7915insA | p.Arg2639ThrfsTer19 | frameshift_variant | 48/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.7869_7870insA | p.Arg2624ThrfsTer19 | frameshift_variant | 48/79 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251098Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135706
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461728Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727168
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | This sequence change creates a premature translational stop signal (p.Arg2639Thrfs*19) in the DNAH5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAH5 are known to be pathogenic (PMID: 11788826, 16627867). This variant is present in population databases (rs749082955, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 16627867). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 454806). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 13, 2020 | - - |
DNAH5-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2023 | The DNAH5 c.7914dupA variant is predicted to result in a frameshift and premature protein termination (p.Arg2639Thrfs*19). This variant has been reported in the compound heterozygous state with a second pathogenic DNAH5 variant in an individual with primary ciliary dyskinesia (Hornef et al. 2006. PubMed ID: 16627867). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in DNAH5 are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at