11-113412755-A-T

Variant names:

• chr11-113412755-A-T
• rs6275
• NM_000795.4:c.939T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000795.4(DRD2):​c.939T>A​(p.His313Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. H313H) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: DRD2 NM_000795.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.939T>A	p.His313Gln	missense	Exon 7 of 8	NP_000786.1	P14416-1
	DRD2	NM_001440368.1		c.936T>A	p.His312Gln	missense	Exon 7 of 8	NP_001427297.1
	DRD2	NM_016574.4		c.852T>A	p.His284Gln	missense	Exon 6 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.939T>A	p.His313Gln	missense	Exon 7 of 8	ENSP00000354859.3	P14416-1
	DRD2	ENST00000542968.5	TSL:1	c.939T>A	p.His313Gln	missense	Exon 6 of 7	ENSP00000442172.1	P14416-1
	DRD2	ENST00000544518.5	TSL:1	c.936T>A	p.His312Gln	missense	Exon 6 of 7	ENSP00000441068.1	F8VUV1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151736 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 90

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151736 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74094

African (AFR) AF: 0.00 AC: 0 AN: 41238

American (AMR) AF: 0.00 AC: 0 AN: 15256

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2086

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.081
DANN	Benign	0.83
DEOGEN2	Benign	0.078	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.45	N
PhyloP100		-0.56
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.077
Sift	Benign	0.68	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.36		Loss of catalytic residue at G314 (P = 0.1636)
MVP		0.57
MPC		0.81
ClinPred		0.052	T
GERP RS		-4.0
Varity_R		0.051
gMVP		0.22
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: -2

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

Other links and lift over

dbSNP: rs6275; hg19: chr11-113283477;