rs80030508

Positions:

• chr11-113424499-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_000795.4(DRD2):​c.153C>A​(p.Gly51=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000838 in 1,614,236 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00086 (1 hom.)
• Consequence: DRD2 NM_000795.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.88

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-113424499-G-T is Benign according to our data. Variant chr11-113424499-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 526229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 90 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD2	NM_000795.4	c.153C>A	p.Gly51=	synonymous_variant	2/8	ENST00000362072.8
DRD2	NM_016574.4	c.153C>A	p.Gly51=	synonymous_variant	2/7
DRD2	XM_017017296.3	c.153C>A	p.Gly51=	synonymous_variant	2/8
DRD2	XM_047426511.1	c.153C>A	p.Gly51=	synonymous_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.153C>A	p.Gly51=	synonymous_variant	2/8	1	NM_000795.4	P4

Frequencies

GnomAD3 genomes AF: 0.000591 AC: 90 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000852

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000672 AC: 169 AN: 251454 Hom.: 1 AF XY: 0.000706 AC XY: 96 AN XY: 135908

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000686

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.000826

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000863 AC: 1262 AN: 1461892 Hom.: 1 Cov.: 31 AF XY: 0.000898 AC XY: 653 AN XY: 727246

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000661

Gnomad4 FIN exome AF: 0.00137

Gnomad4 NFE exome AF: 0.000936

Gnomad4 OTH exome AF: 0.000795

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000617 AC XY: 46 AN XY: 74512

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.000852

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000716 Hom.: 0

Bravo AF: 0.000536

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

DRD2: BP4, BP7 -

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.6
DANN	Benign	0.78

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: rs80030508; hg19: chr11-113295221;