11-113428348-G-C

Variant names:

• chr11-113428348-G-C
• rs12799083
• NM_000795.4:c.-31-3666C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000795.4(DRD2):​c.-31-3666C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 152,308 control chromosomes in the GnomAD database, including 34 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 0.019 (34 hom., cov: 32)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 4 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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0193 (2938/152308) while in subpopulation NFE AF = 0.0284 (1931/68032). AF 95% confidence interval is 0.0273. There are 34 homozygotes in GnomAd4. There are 1403 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2938 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.-31-3666C>G		intron	N/A	NP_000786.1	P14416-1
	DRD2	NM_001440368.1		c.-31-3666C>G		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.-31-3666C>G		intron	N/A	NP_057658.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.-31-3666C>G		intron	N/A	ENSP00000354859.3	P14416-1
	DRD2	ENST00000346454.7	TSL:1	c.-31-3666C>G		intron	N/A	ENSP00000278597.5	P14416-2
	DRD2	ENST00000540600.5	TSL:1	n.35-3666C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2937 AN: 152190 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.00533

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.0301

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0172

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0193 AC: 2938 AN: 152308 Hom.: 34 Cov.: 32 AF XY: 0.0188 AC XY: 1403 AN XY: 74478

African (AFR) AF: 0.00532 AC: 221 AN: 41568

American (AMR) AF: 0.0196 AC: 300 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4822

European-Finnish (FIN) AF: 0.0301 AC: 319 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0284 AC: 1931 AN: 68032

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0118 Hom.: 3

Bravo AF: 0.0177

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.78
PhyloP100		-0.015
Mutation Taster		=100/0	polymorphism

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: rs12799083; hg19: chr11-113299070;