rs4648319

chr11-113443641-G-Achr11-113443641-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.-31-18959C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,162 control chromosomes in the GnomAD database, including 2,342 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 0.16 (2342 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD2	NM_000795.4	c.-31-18959C>T		intron_variant		ENST00000362072.8
DRD2	NM_016574.4	c.-31-18959C>T		intron_variant
DRD2	XM_017017296.3	c.-31-18959C>T		intron_variant
DRD2	XM_047426511.1	c.-31-18959C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.-31-18959C>T		intron_variant		1	NM_000795.4	P4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24180 AN: 152044 Hom.: 2332 Cov.: 33

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.159 AC: 24220 AN: 152162 Hom.: 2342 Cov.: 33 AF XY: 0.167 AC XY: 12402 AN XY: 74370

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.150

Alfa AF: 0.152 Hom.: 1468

Bravo AF: 0.161

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.021
Dann	Benign	0.66

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: rs4648319; hg19: chr11-113314363;