rs2471854

Positions:

• chr11-113428917-G-C
• chr11-113428917-G-T

Variant summary

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

The NM_000795.4(DRD2):​c.-31-4235C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,100 control chromosomes in the GnomAD database, including 3,033 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 0.19 (3033 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-31-4235C>G		intron_variant		ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.-31-4235C>G		intron_variant			NP_057658.2
DRD2	XM_017017296.3	c.-31-4235C>G		intron_variant			XP_016872785.1
DRD2	XM_047426511.1	c.-31-4235C>G		intron_variant			XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-31-4235C>G		intron_variant		1	NM_000795.4	ENSP00000354859	P4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28269 AN: 151982 Hom.: 3021 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.186 AC: 28310 AN: 152100 Hom.: 3033 Cov.: 33 AF XY: 0.194 AC XY: 14393 AN XY: 74354

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.178

Alfa AF: 0.176 Hom.: 325

Bravo AF: 0.192

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.84

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: rs2471854; hg19: chr11-113299639;