rs201984806
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001256864.2(DNAJC6):c.2468G>A(p.Arg823His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,974 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. R823P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001256864.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJC6 | NM_001256864.2 | c.2468G>A | p.Arg823His | missense_variant | 16/19 | ENST00000371069.5 | |
DNAJC6 | NM_014787.4 | c.2297G>A | p.Arg766His | missense_variant | 16/19 | ||
DNAJC6 | NM_001256865.2 | c.2258G>A | p.Arg753His | missense_variant | 17/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJC6 | ENST00000371069.5 | c.2468G>A | p.Arg823His | missense_variant | 16/19 | 1 | NM_001256864.2 | P4 | |
DNAJC6 | ENST00000395325.7 | c.2297G>A | p.Arg766His | missense_variant | 16/19 | 1 | A1 | ||
DNAJC6 | ENST00000263441.11 | c.2258G>A | p.Arg753His | missense_variant | 17/20 | 2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250802Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135536
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461762Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727172
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Juvenile onset Parkinson disease 19A Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 861071). This variant is also known as c.2297G>A. This missense change has been observed in individual(s) with neurodevelopmental disorder (PMID: 28191889). This variant is present in population databases (rs201984806, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 823 of the DNAJC6 protein (p.Arg823His). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2022 | The c.2297G>A (p.R766H) alteration is located in exon 16 (coding exon 16) of the DNAJC6 gene. This alteration results from a G to A substitution at nucleotide position 2297, causing the arginine (R) at amino acid position 766 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at