chr11-113415194-C-T

Variant names:

• chr11-113415194-C-T
• rs12363125
• NM_000795.4:c.723+227G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000795.4(DRD2):​c.723+227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 431,872 control chromosomes in the GnomAD database, including 59,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (16970 hom., cov: 32)
  • Exomes 𝑓: 0.52 (42152 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0550
• Publications: 19 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-113415194-C-T is Benign according to our data. Variant chr11-113415194-C-T is described in ClinVar as Benign. ClinVar VariationId is 1272787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 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.723+227G>A		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.720+227G>A		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.723+227G>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.723+227G>A		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.723+227G>A		intron	N/A	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.720+227G>A		intron	N/A	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64883 AN: 151750 Hom.: 16982 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.520 AC: 145529 AN: 280004 Hom.: 42152 AF XY: 0.523 AC XY: 74295 AN XY: 141952

African (AFR) AF: 0.166 AC: 1339 AN: 8060

American (AMR) AF: 0.375 AC: 3648 AN: 9716

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 6210 AN: 9626

East Asian (EAS) AF: 0.0603 AC: 1435 AN: 23788

South Asian (SAS) AF: 0.385 AC: 2133 AN: 5540

European-Finnish (FIN) AF: 0.504 AC: 11049 AN: 21932

Middle Eastern (MID) AF: 0.561 AC: 754 AN: 1344

European-Non Finnish (NFE) AF: 0.602 AC: 109880 AN: 182388

Other (OTH) AF: 0.516 AC: 9081 AN: 17610

GnomAD4 genome AF: 0.427 AC: 64871 AN: 151868 Hom.: 16970 Cov.: 32 AF XY: 0.417 AC XY: 30969 AN XY: 74214

African (AFR) AF: 0.169 AC: 6990 AN: 41464

American (AMR) AF: 0.388 AC: 5916 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3468

East Asian (EAS) AF: 0.0581 AC: 300 AN: 5160

South Asian (SAS) AF: 0.364 AC: 1747 AN: 4806

European-Finnish (FIN) AF: 0.476 AC: 5003 AN: 10502

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

European-Non Finnish (NFE) AF: 0.601 AC: 40838 AN: 67908

Other (OTH) AF: 0.491 AC: 1034 AN: 2106

Alfa AF: 0.541 Hom.: 69196

Bravo AF: 0.412

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12363125; hg19: chr11-113285916;