rs780839621
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006736.6(DNAJB2):c.71G>A(p.Arg24Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R24W) has been classified as Uncertain significance.
Frequency
Consequence
NM_006736.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJB2 | NM_006736.6 | c.71G>A | p.Arg24Gln | missense_variant | 3/9 | ENST00000336576.10 | |
DNAJB2 | NM_001039550.2 | c.71G>A | p.Arg24Gln | missense_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJB2 | ENST00000336576.10 | c.71G>A | p.Arg24Gln | missense_variant | 3/9 | 1 | NM_006736.6 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251154Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135784
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461548Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727082
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neuronopathy, distal hereditary motor, autosomal recessive 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 17, 2018 | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DNAJB2-related disease. This sequence change replaces arginine with glutamine at codon 24 of the DNAJB2 protein (p.Arg24Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at