rs754919042
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001080463.2(DYNC2H1):c.5495C>A(p.Ser1832Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,082 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S1832S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001080463.2 stop_gained
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 |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.5495C>A | p.Ser1832Ter | stop_gained | 35/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.5495C>A | p.Ser1832Ter | stop_gained | 35/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.5495C>A | p.Ser1832Ter | stop_gained | 35/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.5495C>A | p.Ser1832Ter | stop_gained | 35/89 | 1 | NM_001377.3 | P3 | |
DYNC2H1 | ENST00000334267.11 | c.2205+38823C>A | intron_variant | 1 | |||||
DYNC2H1 | ENST00000649323.1 | c.*3040C>A | 3_prime_UTR_variant, NMD_transcript_variant | 33/51 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1448082Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 720260
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 06, 2023 | This sequence change creates a premature translational stop signal (p.Ser1832*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 238272). For these reasons, this variant has been classified as Pathogenic. - |
Asphyxiating thoracic dystrophy 3 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 08, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at