rs142108185
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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R551C) has been classified 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.1652G>A | p.Arg551His | missense_variant | 17/23 | ENST00000444659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.1652G>A | p.Arg551His | missense_variant | 17/23 | 5 | NM_001386795.1 | P3 |
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
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 21, 2019 | 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) - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Left ventricular noncompaction 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 07, 2023 | 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%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 191652). This missense change has been observed in individual(s) with sudden unexplained death (PMID: 33789662). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at