11-113464537-A-G

Variant names:

• chr11-113464537-A-G
• rs11214613
• NM_000795.4:c.-32+10539T>C

Variant summary

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

The NM_000795.4(DRD2):​c.-32+10539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,174 control chromosomes in the GnomAD database, including 49,612 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 0.79 (49612 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 15 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-32+10539T>C		intron_variant	Intron 1 of 7	ENST00000362072.8	NP_000786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-32+10539T>C		intron_variant	Intron 1 of 7	1	NM_000795.4	ENSP00000354859.3
DRD2	ENST00000346454.7	c.-32+10539T>C		intron_variant	Intron 1 of 6	1		ENSP00000278597.5
DRD2	ENST00000540600.5	n.34+11121T>C		intron_variant	Intron 1 of 5	1
DRD2	ENST00000542616.1	c.-32+9693T>C		intron_variant	Intron 2 of 2	4		ENSP00000441474.1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119429 AN: 152056 Hom.: 49592 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.785 AC: 119498 AN: 152174 Hom.: 49612 Cov.: 33 AF XY: 0.792 AC XY: 58924 AN XY: 74400

African (AFR) AF: 0.488 AC: 20220 AN: 41462

American (AMR) AF: 0.854 AC: 13065 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3261 AN: 3472

East Asian (EAS) AF: 0.870 AC: 4502 AN: 5176

South Asian (SAS) AF: 0.886 AC: 4271 AN: 4822

European-Finnish (FIN) AF: 0.942 AC: 10004 AN: 10620

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61370 AN: 68008

Other (OTH) AF: 0.832 AC: 1758 AN: 2112

Alfa AF: 0.834 Hom.: 6806

Bravo AF: 0.767

Asia WGS AF: 0.834 AC: 2902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.86
PhyloP100		-0.12
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: rs11214613; hg19: chr11-113335259;