11-113462949-A-T

Position:

• chr11-113462949-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000362072.8(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 ENST00000362072.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-32+12127T>A		intron_variant		ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.-32+12127T>A		intron_variant			NP_057658.2
DRD2	XM_017017296.3	c.-32+11281T>A		intron_variant			XP_016872785.1
DRD2	XM_047426511.1	c.-32+11281T>A		intron_variant			XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-32+12127T>A		intron_variant		1	NM_000795.4	ENSP00000354859	P4
DRD2	ENST00000346454.7	c.-32+12127T>A		intron_variant		1		ENSP00000278597
DRD2	ENST00000540600.5	n.34+12709T>A		intron_variant, non_coding_transcript_variant		1
DRD2	ENST00000542616.1	c.-32+11281T>A		intron_variant		4		ENSP00000441474

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

Gnomad4 AFR AF: 0.0829

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0290

Gnomad4 OTH AF: 0.0748

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs10891552; hg19: chr11-113333671;