rs12808482

Variant names:

• chr11-113424276-T-A
• rs12808482
• NM_000795.4:c.285+91A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-113424276-T-A
• chr11-113424276-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000795.4(DRD2):​c.285+91A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,430,594 control chromosomes in the GnomAD database, including 226,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (17499 hom., cov: 32)
  • Exomes 𝑓: 0.56 (208553 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0810
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-113424276-T-A is Benign according to our data. Variant chr11-113424276-T-A is described in ClinVar as Benign. ClinVar VariationId is 1289649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.285+91A>T		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.289+87A>T		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.285+91A>T		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.285+91A>T		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.285+91A>T		intron	N/A	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.289+87A>T		intron	N/A	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67383 AN: 151886 Hom.: 17510 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.557 AC: 711755 AN: 1278590 Hom.: 208553 AF XY: 0.554 AC XY: 351763 AN XY: 635468

African (AFR) AF: 0.215 AC: 6230 AN: 28968

American (AMR) AF: 0.322 AC: 11542 AN: 35808

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 15784 AN: 24200

East Asian (EAS) AF: 0.0604 AC: 2134 AN: 35316

South Asian (SAS) AF: 0.401 AC: 30751 AN: 76720

European-Finnish (FIN) AF: 0.504 AC: 24038 AN: 47738

Middle Eastern (MID) AF: 0.557 AC: 2903 AN: 5208

European-Non Finnish (NFE) AF: 0.607 AC: 589621 AN: 970648

Other (OTH) AF: 0.533 AC: 28752 AN: 53984

GnomAD4 genome AF: 0.443 AC: 67379 AN: 152004 Hom.: 17499 Cov.: 32 AF XY: 0.433 AC XY: 32162 AN XY: 74296

African (AFR) AF: 0.223 AC: 9256 AN: 41440

American (AMR) AF: 0.394 AC: 6025 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2237 AN: 3470

East Asian (EAS) AF: 0.0583 AC: 301 AN: 5164

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4810

European-Finnish (FIN) AF: 0.476 AC: 5024 AN: 10558

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40908 AN: 67964

Other (OTH) AF: 0.501 AC: 1057 AN: 2108

Alfa AF: 0.376 Hom.: 1126

Bravo AF: 0.431

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		-0.081
PromoterAI		0.0019	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: rs12808482; hg19: chr11-113294998;