NM_000795.4:c.-31-4235C>G

Variant names:

• chr11-113428917-G-C
• rs2471854
• NM_000795.4:c.-31-4235C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.82).
• 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 rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-31-4235C>G		intron_variant	Intron 1 of 7	ENST00000362072.8	NP_000786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-31-4235C>G		intron_variant	Intron 1 of 7	1	NM_000795.4	ENSP00000354859.3

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

African (AFR) AF: 0.163 AC: 6773 AN: 41498

American (AMR) AF: 0.277 AC: 4236 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2159 AN: 5148

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4822

European-Finnish (FIN) AF: 0.212 AC: 2241 AN: 10580

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10633 AN: 67978

Other (OTH) AF: 0.178 AC: 376 AN: 2110

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
PhyloP100		0.45
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: rs2471854; hg19: chr11-113299639; COSMIC: COSV107407558; COSMIC: COSV107407558;