rs4938019

Positions:

• chr11-113470669-T-C
• chr11-113470669-T-G

Variant summary

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

The NM_000795.4(DRD2):​c.-32+4407A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,242 control chromosomes in the GnomAD database, including 2,490 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 0.17 (2490 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-32+4407A>G		intron_variant		ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.-32+4407A>G		intron_variant			NP_057658.2
DRD2	XM_017017296.3	c.-32+3561A>G		intron_variant			XP_016872785.1
DRD2	XM_047426511.1	c.-32+3561A>G		intron_variant			XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-32+4407A>G		intron_variant		1	NM_000795.4	ENSP00000354859	P4
DRD2	ENST00000346454.7	c.-32+4407A>G		intron_variant		1		ENSP00000278597
DRD2	ENST00000540600.5	n.34+4989A>G		intron_variant, non_coding_transcript_variant		1
DRD2	ENST00000542616.1	c.-32+3561A>G		intron_variant		4		ENSP00000441474

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25386 AN: 152124 Hom.: 2480 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.167 AC: 25429 AN: 152242 Hom.: 2490 Cov.: 33 AF XY: 0.174 AC XY: 12947 AN XY: 74418

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.165

Alfa AF: 0.147 Hom.: 956

Bravo AF: 0.171

Asia WGS AF: 0.276 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.51

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: rs4938019; hg19: chr11-113341391;