rs1076563

chr11-113425187-A-Cchr11-113425187-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD2	NM_000795.4	c.-31-505T>G		intron_variant		ENST00000362072.8
DRD2	NM_016574.4	c.-31-505T>G		intron_variant
DRD2	XM_017017296.3	c.-31-505T>G		intron_variant
DRD2	XM_047426511.1	c.-31-505T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.-31-505T>G		intron_variant		1	NM_000795.4	P4

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

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.500

Alfa AF: 0.540 Hom.: 9940

Bravo AF: 0.430

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.026
Dann	Benign	0.50

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: rs1076563; hg19: chr11-113295909;