NM_000795.4:c.533-496G>A

Variant names:

• chr11-113416107-C-T
• rs2734837
• NM_000795.4:c.533-496G>A

Variant summary

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

The NM_000795.4(DRD2):​c.533-496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,088 control chromosomes in the GnomAD database, including 19,168 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 0.48 (19168 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819
• Publications: 12 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=-0.93).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.533-496G>A		intron	N/A	NP_000786.1	P14416-1
	DRD2	NM_001440368.1		c.530-496G>A		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.533-496G>A		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.533-496G>A		intron	N/A	ENSP00000354859.3	P14416-1
	DRD2	ENST00000542968.5	TSL:1	c.533-496G>A		intron	N/A	ENSP00000442172.1	P14416-1
	DRD2	ENST00000544518.5	TSL:1	c.530-496G>A		intron	N/A	ENSP00000441068.1	F8VUV1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73026 AN: 151970 Hom.: 19177 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.480 AC: 73028 AN: 152088 Hom.: 19168 Cov.: 33 AF XY: 0.468 AC XY: 34824 AN XY: 74334

African (AFR) AF: 0.353 AC: 14623 AN: 41478

American (AMR) AF: 0.405 AC: 6194 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2237 AN: 3468

East Asian (EAS) AF: 0.0586 AC: 303 AN: 5174

South Asian (SAS) AF: 0.364 AC: 1758 AN: 4824

European-Finnish (FIN) AF: 0.477 AC: 5031 AN: 10558

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40945 AN: 67980

Other (OTH) AF: 0.529 AC: 1119 AN: 2116

Alfa AF: 0.532 Hom.: 2934

Bravo AF: 0.471

Asia WGS AF: 0.216 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.56
PhyloP100		-0.82
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: rs2734837; hg19: chr11-113286829;