NM_000795.4:c.-31-23004A>G

Variant names:

• chr11-113447686-T-C
• rs4936270
• NM_000795.4:c.-31-23004A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000795.4(DRD2):​c.-31-23004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,048 control chromosomes in the GnomAD database, including 48,872 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (48855 hom., cov: 30)
  • Exomes 𝑓: 0.80 (17 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

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.-31-23004A>G		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.-31-23004A>G		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.-31-23004A>G		intron	N/A	NP_057658.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.-31-23004A>G		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000346454.7	TSL:1	c.-31-23004A>G		intron	N/A	ENSP00000278597.5
	DRD2	ENST00000540600.5	TSL:1	n.35-23004A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118271 AN: 151876 Hom.: 48837 Cov.: 30

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.828

GnomAD4 exome AF: 0.796 AC: 43 AN: 54 Hom.: 17 Cov.: 0 AF XY: 0.842 AC XY: 32 AN XY: 38

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.857 AC: 36 AN: 42

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.779 AC: 118335 AN: 151994 Hom.: 48855 Cov.: 30 AF XY: 0.785 AC XY: 58358 AN XY: 74314

African (AFR) AF: 0.475 AC: 19679 AN: 41388

American (AMR) AF: 0.852 AC: 13014 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3261 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4335 AN: 5120

South Asian (SAS) AF: 0.885 AC: 4265 AN: 4818

European-Finnish (FIN) AF: 0.942 AC: 9984 AN: 10602

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 61019 AN: 68000

Other (OTH) AF: 0.825 AC: 1740 AN: 2108

Alfa AF: 0.866 Hom.: 29611

Bravo AF: 0.759

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.32
DANN	Benign	0.66
PhyloP100		-3.5
PromoterAI		-0.0070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4936270; hg19: chr11-113318408;