rs6275

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-113412755-A-C
• chr11-113412755-A-G
• chr11-113412755-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000795.4(DRD2):​c.939T>G​(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. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. H313H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.939T>G	p.His313Gln	missense	Exon 7 of 8	NP_000786.1
	DRD2	NM_001440368.1		c.936T>G	p.His312Gln	missense	Exon 7 of 8	NP_001427297.1
	DRD2	NM_016574.4		c.852T>G	p.His284Gln	missense	Exon 6 of 7	NP_057658.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.939T>G	p.His313Gln	missense	Exon 7 of 8	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.939T>G	p.His313Gln	missense	Exon 6 of 7	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.936T>G	p.His312Gln	missense	Exon 6 of 7	ENSP00000441068.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 90

GnomAD4 genome Cov.: 31

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	5.2
DANN	Benign	0.83
DEOGEN2	Benign	0.078	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.040	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		0.53
MPC		0.81
ClinPred		0.050	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)		0.81		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.81		Position offset: -1

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

Other links and lift over

dbSNP: rs6275; hg19: chr11-113283477;