rs757922501
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_001080463.2(DYNC2H1):āc.11510A>Gā(p.Tyr3837Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000159 in 1,569,468 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 Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. Y3837Y) has been classified as Likely benign.
Frequency
Consequence
NM_001080463.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.11510A>G | p.Tyr3837Cys | missense_variant | 79/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.11489A>G | p.Tyr3830Cys | missense_variant | 78/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.11510A>G | p.Tyr3837Cys | missense_variant | 79/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.11489A>G | p.Tyr3830Cys | missense_variant | 78/89 | 1 | NM_001377.3 | P3 | |
DYNC2H1 | ENST00000334267.11 | c.2206-128116A>G | intron_variant | 1 | |||||
DYNC2H1 | ENST00000528670.5 | c.668A>G | p.Tyr223Cys | missense_variant, NMD_transcript_variant | 6/17 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000949 AC: 2AN: 210808Hom.: 0 AF XY: 0.00000884 AC XY: 1AN XY: 113178
GnomAD4 exome AF: 0.0000155 AC: 22AN: 1417300Hom.: 0 Cov.: 25 AF XY: 0.0000171 AC XY: 12AN XY: 703672
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 11, 2015 | - - |
Jeune thoracic dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 3837 of the DYNC2H1 protein (p.Tyr3837Cys). This variant is present in population databases (rs757922501, gnomAD 0.005%). 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: 435007). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at