11-113418344-C-T

Variant names:

• chr11-113418344-C-T
• rs2075654
• NM_000795.4:c.286-208G>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.286-208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,172 control chromosomes in the GnomAD database, including 2,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2391 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.354
• Publications: 26 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=-0.86).
• BP6: Variant 11-113418344-C-T is Benign according to our data. Variant chr11-113418344-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 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.286-208G>A		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.290-215G>A		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.286-208G>A		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.286-208G>A		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.286-208G>A		intron	N/A	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.290-215G>A		intron	N/A	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22726 AN: 152054 Hom.: 2382 Cov.: 33

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.150 AC: 22750 AN: 152172 Hom.: 2391 Cov.: 33 AF XY: 0.158 AC XY: 11741 AN XY: 74374

African (AFR) AF: 0.0411 AC: 1708 AN: 41540

American (AMR) AF: 0.262 AC: 3999 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2132 AN: 5148

South Asian (SAS) AF: 0.265 AC: 1274 AN: 4814

European-Finnish (FIN) AF: 0.212 AC: 2240 AN: 10580

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10608 AN: 68016

Other (OTH) AF: 0.148 AC: 313 AN: 2110

Alfa AF: 0.137 Hom.: 296

Bravo AF: 0.151

Asia WGS AF: 0.312 AC: 1084 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	-0.86
CADD	Benign	5.4
DANN	Benign	0.45
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2075654; hg19: chr11-113289066;