rs766816050
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001080463.2(DYNC2H1):c.12487_12490del(p.Asp4163LysfsTer45) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,686 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. V4162V) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001080463.2 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 |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.12487_12490del | p.Asp4163LysfsTer45 | frameshift_variant | 87/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.12466_12469del | p.Asp4156LysfsTer45 | frameshift_variant | 86/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000375735.7 | c.12466_12469del | p.Asp4156LysfsTer45 | frameshift_variant | 86/89 | 1 | NM_001377.3 | P3 | |
DYNC2H1 | ENST00000650373.2 | c.12487_12490del | p.Asp4163LysfsTer45 | frameshift_variant | 87/90 | NM_001080463.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248758Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134972
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1460626Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 726596
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74272
ClinVar
Submissions by phenotype
Asphyxiating thoracic dystrophy 3 Pathogenic:2
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
Jeune thoracic dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 17, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 446597). This premature translational stop signal has been observed in individual(s) with short-rib polydactyly syndrome (PMID: 29068549). This variant is present in population databases (rs766816050, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Asp4163Lysfs*45) in the DYNC2H1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734, 33755199). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at