NM_001080463.2:c.12577G>A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001080463.2(DYNC2H1):c.12577G>A(p.Glu4193Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,724 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001080463.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.12577G>A | p.Glu4193Lys | missense_variant | Exon 87 of 90 | ENST00000650373.2 | NP_001073932.1 | |
DYNC2H1 | NM_001377.3 | c.12556G>A | p.Glu4186Lys | missense_variant | Exon 86 of 89 | ENST00000375735.7 | NP_001368.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.12577G>A | p.Glu4193Lys | missense_variant | Exon 87 of 90 | NM_001080463.2 | ENSP00000497174.1 | |||
DYNC2H1 | ENST00000375735.7 | c.12556G>A | p.Glu4186Lys | missense_variant | Exon 86 of 89 | 1 | NM_001377.3 | ENSP00000364887.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248806Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134988
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460724Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726680
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy Uncertain:1
This sequence change replaces glutamic acid with lysine at codon 4193 of the DYNC2H1 protein (p.Glu4193Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. 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