rs758884516
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_000795.4(DRD2):c.880C>T(p.Arg294Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,374 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
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
DRD2
NM_000795.4 missense
NM_000795.4 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 2.49
Genes affected
DRD2 (HGNC:3023): (dopamine receptor D2) This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, DRD2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.32111308).
BS2
?
High AC in GnomAdExome4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DRD2 | NM_000795.4 | c.880C>T | p.Arg294Trp | missense_variant | 7/8 | ENST00000362072.8 | |
DRD2 | NM_016574.4 | c.793C>T | p.Arg265Trp | missense_variant | 6/7 | ||
DRD2 | XM_017017296.3 | c.880C>T | p.Arg294Trp | missense_variant | 7/8 | ||
DRD2 | XM_047426511.1 | c.793C>T | p.Arg265Trp | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DRD2 | ENST00000362072.8 | c.880C>T | p.Arg294Trp | missense_variant | 7/8 | 1 | NM_000795.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249984Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135118
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461240Hom.: 0 Cov.: 36 AF XY: 0.0000165 AC XY: 12AN XY: 726854
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74310
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dystonic disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 18, 2018 | 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 DRD2-related disease. This variant is present in population databases (rs758884516, ExAC 0.006%). This sequence change replaces arginine with tryptophan at codon 294 of the DRD2 protein (p.Arg294Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
P;D;D;D;.
Vest4
MutPred
0.40
.;Loss of loop (P = 0.0374);.;Loss of loop (P = 0.0374);.;
MVP
MPC
1.8
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at