rs376186482

Variant names:

• chr11-113410767-A-G
• rs376186482
• NM_000795.4:c.1292T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-113410767-A-G
• chr11-113410767-A-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000795.4(DRD2):​c.1292T>C​(p.Ile431Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: DRD2 NM_000795.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 7.29
• Publications: 0 publications found

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]

ENSG00000256757 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12552765).
• BS2: High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.1292T>C	p.Ile431Thr	missense	Exon 8 of 8	NP_000786.1	P14416-1
	DRD2	NM_001440368.1		c.1289T>C	p.Ile430Thr	missense	Exon 8 of 8	NP_001427297.1
	DRD2	NM_016574.4		c.1205T>C	p.Ile402Thr	missense	Exon 7 of 7	NP_057658.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.1292T>C	p.Ile431Thr	missense	Exon 8 of 8	ENSP00000354859.3	P14416-1
	DRD2	ENST00000542968.5	TSL:1	c.1292T>C	p.Ile431Thr	missense	Exon 7 of 7	ENSP00000442172.1	P14416-1
	DRD2	ENST00000544518.5	TSL:1	c.1289T>C	p.Ile430Thr	missense	Exon 7 of 7	ENSP00000441068.1	F8VUV1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251448 AF XY: 0.0000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000527 AC: 77 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.0000633 AC XY: 46 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1112012

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74480

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000576 AC: 7

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Dystonic disorder (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-1.5	N
PhyloP100		7.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.27
Sift	Benign	0.32	T
Sift4G	Benign	0.48	T
Polyphen		0.32	B
Vest4		0.57
MVP		0.54
MPC		1.0
ClinPred		0.16	T
GERP RS		5.5
Varity_R		0.44
gMVP		0.79
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376186482; hg19: chr11-113281489;