rs35608204

Positions:

• chr11-113415071-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000795.4(DRD2):​c.723+350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 152,252 control chromosomes in the GnomAD database, including 36 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 0.018 (36 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399

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]

DRD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0184 (2800/152252) while in subpopulation NFE AF= 0.0272 (1852/68020). AF 95% confidence interval is 0.0262. There are 36 homozygotes in gnomad4. There are 1320 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2800 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.723+350T>C		intron_variant		ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.723+350T>C		intron_variant			NP_057658.2
DRD2	XM_017017296.3	c.723+350T>C		intron_variant			XP_016872785.1
DRD2	XM_047426511.1	c.723+350T>C		intron_variant			XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.723+350T>C		intron_variant		1	NM_000795.4	ENSP00000354859.3

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2804 AN: 152136 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.00473

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0234

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

GnomAD4 genome AF: 0.0184 AC: 2800 AN: 152252 Hom.: 36 Cov.: 33 AF XY: 0.0177 AC XY: 1320 AN XY: 74440

Gnomad4 AFR AF: 0.00469

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.0196

Gnomad4 NFE AF: 0.0272

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0256 Hom.: 13

Bravo AF: 0.0184

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
DANN	Benign	0.82

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: rs35608204; hg19: chr11-113285793;