rs11608185

Variant names:

• chr11-113424254-T-C
• rs11608185
• NM_000795.4:c.285+113A>G

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+113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,243,088 control chromosomes in the GnomAD database, including 195,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (17494 hom., cov: 32)
  • Exomes 𝑓: 0.56 (177916 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.199
• Publications: 13 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=-0.84).
• BP6: Variant 11-113424254-T-C is Benign according to our data. Variant chr11-113424254-T-C is described in ClinVar as Benign. ClinVar VariationId is 1249149.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.285+113A>G		intron	N/A	NP_000786.1	P14416-1
	DRD2	NM_001440368.1		c.289+109A>G		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.285+113A>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.285+113A>G		intron	N/A	ENSP00000354859.3	P14416-1
	DRD2	ENST00000542968.5	TSL:1	c.285+113A>G		intron	N/A	ENSP00000442172.1	P14416-1
	DRD2	ENST00000544518.5	TSL:1	c.289+109A>G		intron	N/A	ENSP00000441068.1	F8VUV1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67383 AN: 151916 Hom.: 17505 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: 0.0585

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.556 AC: 606187 AN: 1091054 Hom.: 177916 AF XY: 0.552 AC XY: 302335 AN XY: 547326

African (AFR) AF: 0.219 AC: 5423 AN: 24788

American (AMR) AF: 0.327 AC: 10800 AN: 33052

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 14730 AN: 22496

East Asian (EAS) AF: 0.0609 AC: 2069 AN: 33978

South Asian (SAS) AF: 0.403 AC: 28312 AN: 70332

European-Finnish (FIN) AF: 0.503 AC: 22187 AN: 44070

Middle Eastern (MID) AF: 0.564 AC: 2456 AN: 4356

European-Non Finnish (NFE) AF: 0.611 AC: 494702 AN: 810312

Other (OTH) AF: 0.535 AC: 25508 AN: 47670

GnomAD4 genome AF: 0.443 AC: 67379 AN: 152034 Hom.: 17494 Cov.: 32 AF XY: 0.433 AC XY: 32164 AN XY: 74312

African (AFR) AF: 0.223 AC: 9261 AN: 41460

American (AMR) AF: 0.394 AC: 6024 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2239 AN: 3470

East Asian (EAS) AF: 0.0580 AC: 300 AN: 5168

South Asian (SAS) AF: 0.365 AC: 1758 AN: 4818

European-Finnish (FIN) AF: 0.476 AC: 5028 AN: 10568

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

European-Non Finnish (NFE) AF: 0.602 AC: 40897 AN: 67946

Other (OTH) AF: 0.500 AC: 1058 AN: 2114

Alfa AF: 0.516 Hom.: 2746

Bravo AF: 0.430

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

ClinVar submissions

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	-0.84
CADD	Benign	0.64
DANN	Benign	0.70
PhyloP100		-0.20
PromoterAI		0.032	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: rs11608185; hg19: chr11-113294976;