rs778594253
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_001080463.2(DYNC2H1):āc.954A>Cā(p.Lys318Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. K318K) has been classified as Likely benign.
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.954A>C | p.Lys318Asn | missense_variant | 6/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.954A>C | p.Lys318Asn | missense_variant | 6/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.954A>C | p.Lys318Asn | missense_variant | 6/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.954A>C | p.Lys318Asn | missense_variant | 6/89 | 1 | NM_001377.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248810Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135012
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460826Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726662
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 09, 2023 | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 318 of the DYNC2H1 protein (p.Lys318Asn). This variant is present in population databases (rs778594253, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DYNC2H1 protein function. 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