NM_000795.4:c.286-2485A>C

Variant names:

• chr11-113420621-T-G
• rs2734835
• NM_000795.4:c.286-2485A>C

Variant summary

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

The NM_000795.4(DRD2):​c.286-2485A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,132 control chromosomes in the GnomAD database, including 16,999 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 0.43 (16999 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 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.286-2485A>C		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.290-2492A>C		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.286-2485A>C		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.286-2485A>C		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.286-2485A>C		intron	N/A	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.290-2492A>C		intron	N/A	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64835 AN: 152014 Hom.: 17011 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.426 AC: 64817 AN: 152132 Hom.: 16999 Cov.: 33 AF XY: 0.416 AC XY: 30959 AN XY: 74362

African (AFR) AF: 0.164 AC: 6785 AN: 41498

American (AMR) AF: 0.389 AC: 5940 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2232 AN: 3468

East Asian (EAS) AF: 0.0585 AC: 303 AN: 5180

South Asian (SAS) AF: 0.365 AC: 1759 AN: 4822

European-Finnish (FIN) AF: 0.476 AC: 5040 AN: 10582

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40909 AN: 67976

Other (OTH) AF: 0.491 AC: 1036 AN: 2112

Alfa AF: 0.506 Hom.: 2712

Bravo AF: 0.411

Asia WGS AF: 0.202 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.63
PhyloP100		-0.81
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: rs2734835; hg19: chr11-113291343;