rs754698253
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001369.3(DNAH5):c.3905del(p.Leu1302ArgfsTer19) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,940 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. L1302L) 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 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.3905del | p.Leu1302ArgfsTer19 | frameshift_variant | 25/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.3905del | p.Leu1302ArgfsTer19 | frameshift_variant | 25/79 | 1 | NM_001369.3 | P4 | |
ENST00000503244.2 | n.253+7367del | intron_variant, non_coding_transcript_variant | 4 | ||||||
DNAH5 | ENST00000681290.1 | c.3860del | p.Leu1287ArgfsTer19 | frameshift_variant | 25/79 | A1 | |||
ENST00000637153.1 | n.213+7407del | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251140Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135708
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461798Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 727212
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | This sequence change creates a premature translational stop signal (p.Leu1302Argfs*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 (rs754698253, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 2506606, 16627867). ClinVar contains an entry for this variant (Variation ID: 454772). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely pathogenic, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Aug 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at