NM_000795.4:c.1139-134T>G

Variant names:

• chr11-113411054-A-C
• rs2734841
• NM_000795.4:c.1139-134T>G

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.1139-134T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 916,124 control chromosomes in the GnomAD database, including 206,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (28591 hom., cov: 31)
  • Exomes 𝑓: 0.68 (177447 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.27
• Publications: 14 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]

ENSG00000256757 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-113411054-A-C is Benign according to our data. Variant chr11-113411054-A-C is described in ClinVar as Benign. ClinVar VariationId is 1238634.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 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.1139-134T>G		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.1136-134T>G		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.1052-134T>G		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.1139-134T>G		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.1139-134T>G		intron	N/A	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.1136-134T>G		intron	N/A	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91332 AN: 151762 Hom.: 28585 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.639

GnomAD4 exome AF: 0.676 AC: 516362 AN: 764244 Hom.: 177447 AF XY: 0.675 AC XY: 260853 AN XY: 386402

African (AFR) AF: 0.409 AC: 7496 AN: 18346

American (AMR) AF: 0.655 AC: 14634 AN: 22326

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 10370 AN: 15936

East Asian (EAS) AF: 0.440 AC: 14255 AN: 32426

South Asian (SAS) AF: 0.646 AC: 34265 AN: 53066

European-Finnish (FIN) AF: 0.668 AC: 26560 AN: 39732

Middle Eastern (MID) AF: 0.624 AC: 1691 AN: 2712

European-Non Finnish (NFE) AF: 0.705 AC: 383397 AN: 543534

Other (OTH) AF: 0.655 AC: 23694 AN: 36166

GnomAD4 genome AF: 0.602 AC: 91365 AN: 151880 Hom.: 28591 Cov.: 31 AF XY: 0.599 AC XY: 44508 AN XY: 74254

African (AFR) AF: 0.426 AC: 17664 AN: 41424

American (AMR) AF: 0.618 AC: 9433 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2274 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2340 AN: 5110

South Asian (SAS) AF: 0.628 AC: 3019 AN: 4804

European-Finnish (FIN) AF: 0.658 AC: 6960 AN: 10574

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47508 AN: 67912

Other (OTH) AF: 0.636 AC: 1341 AN: 2108

Alfa AF: 0.657 Hom.: 48618

Bravo AF: 0.595

Asia WGS AF: 0.531 AC: 1848 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0020
DANN	Benign	0.58
PhyloP100		-3.3
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: rs2734841; hg19: chr11-113281776;