rs746195428
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001377.3(DYNC2H1):c.7663G>A(p.Val2555Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001377.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.7663G>A | p.Val2555Met | missense_variant | Exon 47 of 90 | ENST00000650373.2 | NP_001073932.1 | |
DYNC2H1 | NM_001377.3 | c.7663G>A | p.Val2555Met | missense_variant | Exon 47 of 89 | ENST00000375735.7 | NP_001368.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.7663G>A | p.Val2555Met | missense_variant | Exon 47 of 90 | NM_001080463.2 | ENSP00000497174.1 | |||
DYNC2H1 | ENST00000375735.7 | c.7663G>A | p.Val2555Met | missense_variant | Exon 47 of 89 | 1 | NM_001377.3 | ENSP00000364887.2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1435844Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 713358
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74294
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy Pathogenic:2
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not specified Uncertain:1
Variant summary: DYNC2H1 c.7663G>A (p.Val2555Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 244838 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.7663G>A has been reported in the literature in individuals affected with Asphyxiating thoracic dystrophy (Schmidts_2013, Zhang_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23456818, 29068549). ClinVar contains an entry for this variant (Variation ID: 446589). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at