chr11-113425187-A-C

Variant names:

• chr11-113425187-A-C
• rs1076563
• NM_000795.4:c.-31-505T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000795.4(DRD2):​c.-31-505T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,088 control chromosomes in the GnomAD database, including 17,472 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (17472 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 34 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• 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.-31-505T>G		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.-31-505T>G		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.-31-505T>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.-31-505T>G		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000346454.7	TSL:1	c.-31-505T>G		intron	N/A	ENSP00000278597.5
	DRD2	ENST00000540600.5	TSL:1	n.35-505T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67308 AN: 151970 Hom.: 17483 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.443 AC: 67302 AN: 152088 Hom.: 17472 Cov.: 33 AF XY: 0.432 AC XY: 32131 AN XY: 74346

African (AFR) AF: 0.222 AC: 9213 AN: 41484

American (AMR) AF: 0.393 AC: 6000 AN: 15266

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

East Asian (EAS) AF: 0.0583 AC: 302 AN: 5180

South Asian (SAS) AF: 0.364 AC: 1755 AN: 4820

European-Finnish (FIN) AF: 0.475 AC: 5018 AN: 10568

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

European-Non Finnish (NFE) AF: 0.602 AC: 40908 AN: 67986

Other (OTH) AF: 0.500 AC: 1057 AN: 2112

Alfa AF: 0.548 Hom.: 41338

Bravo AF: 0.430

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.026
DANN	Benign	0.50
PhyloP100		-1.8
PromoterAI		-0.0022	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: rs1076563; hg19: chr11-113295909;