chr18-34863971-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3BP4BS2
The NM_001386795.1(DTNA):c.1652G>A(p.Arg551His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,609,052 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_001386795.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.1652G>A | p.Arg551His | missense_variant | Exon 17 of 23 | ENST00000444659.6 | NP_001373724.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.1652G>A | p.Arg551His | missense_variant | Exon 17 of 23 | 5 | NM_001386795.1 | ENSP00000405819.2 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000941 AC: 23AN: 244444Hom.: 0 AF XY: 0.0000834 AC XY: 11AN XY: 131898
GnomAD4 exome AF: 0.000139 AC: 203AN: 1456886Hom.: 0 Cov.: 31 AF XY: 0.000137 AC XY: 99AN XY: 724244
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152166Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:5
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Reported in a cohort of patients not selected for arrhythmia, cardiomyopathy, or family history of sudden cardiac death, although no clinical or segregation data were provided (Ng et al., 2013).; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23861362) -
Left ventricular noncompaction 1 Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 524 of the DTNA protein (p.Arg524His). This variant is present in population databases (rs142108185, gnomAD 0.02%). This missense change has been observed in individual(s) with sudden unexplained death (PMID: 33789662). ClinVar contains an entry for this variant (Variation ID: 191652). 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 disruptive. 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