11-103184898-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5
The NM_001377.3(DYNC2H1):c.6480T>A(p.Asn2160Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000534 in 1,609,920 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001377.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.6480T>A | p.Asn2160Lys | missense_variant, splice_region_variant | Exon 41 of 90 | ENST00000650373.2 | NP_001073932.1 | |
DYNC2H1 | NM_001377.3 | c.6480T>A | p.Asn2160Lys | missense_variant, splice_region_variant | Exon 41 of 89 | ENST00000375735.7 | NP_001368.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.6480T>A | p.Asn2160Lys | missense_variant, splice_region_variant | Exon 41 of 90 | NM_001080463.2 | ENSP00000497174.1 | |||
DYNC2H1 | ENST00000375735.7 | c.6480T>A | p.Asn2160Lys | missense_variant, splice_region_variant | Exon 41 of 89 | 1 | NM_001377.3 | ENSP00000364887.2 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151892Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000363 AC: 9AN: 248048Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134560
GnomAD4 exome AF: 0.0000549 AC: 80AN: 1458028Hom.: 0 Cov.: 30 AF XY: 0.0000552 AC XY: 40AN XY: 725288
GnomAD4 genome AF: 0.0000395 AC: 6AN: 151892Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74186
ClinVar
Submissions by phenotype
Asphyxiating thoracic dystrophy 3 Pathogenic:3
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Apr 27, 2022 | PM1, PM2, PM3 - |
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Jeune thoracic dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 04, 2024 | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 2160 of the DYNC2H1 protein (p.Asn2160Lys). This variant is present in population databases (rs775426647, gnomAD 0.008%). This missense change has been observed in individual(s) with DYNC2H1-related conditions (PMID: 29068549). ClinVar contains an entry for this variant (Variation ID: 446572). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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