11-113462949-A-T

Variant names:

• chr11-113462949-A-T
• rs10891552
• NM_000795.4:c.-32+12127T>A

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+12127T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 150,460 control chromosomes in the GnomAD database, including 968 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 0.079 (968 hom., cov: 32)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 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.-32+12127T>A		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.-32+12127T>A		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.-32+12127T>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.-32+12127T>A		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000346454.7	TSL:1	c.-32+12127T>A		intron	N/A	ENSP00000278597.5
	DRD2	ENST00000540600.5	TSL:1	n.34+12709T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 11910 AN: 150352 Hom.: 959 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.0265

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0717

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

GnomAD4 genome AF: 0.0794 AC: 11953 AN: 150460 Hom.: 968 Cov.: 32 AF XY: 0.0876 AC XY: 6425 AN XY: 73330

African (AFR) AF: 0.0829 AC: 3382 AN: 40778

American (AMR) AF: 0.186 AC: 2807 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3464

East Asian (EAS) AF: 0.389 AC: 1971 AN: 5070

South Asian (SAS) AF: 0.0563 AC: 268 AN: 4756

European-Finnish (FIN) AF: 0.125 AC: 1282 AN: 10216

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0290 AC: 1966 AN: 67752

Other (OTH) AF: 0.0748 AC: 157 AN: 2098

Alfa AF: 0.0482 Hom.: 48

Bravo AF: 0.0874

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.67
PhyloP100		0.061
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: rs10891552; hg19: chr11-113333671;