rs1800499

Positions:

• chr11-113416972-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000795.4(DRD2):​c.423G>A​(p.Leu141Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 1,614,058 control chromosomes in the GnomAD database, including 1,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (66 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1023 hom.)
• Consequence: DRD2 NM_000795.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.108

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 11-113416972-C-T is Benign according to our data. Variant chr11-113416972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 238185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-113416972-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.108 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0234 (3558/152318) while in subpopulation SAS AF= 0.0348 (168/4822). AF 95% confidence interval is 0.0334. There are 66 homozygotes in gnomad4. There are 1732 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3558 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.423G>A	p.Leu141Leu	synonymous_variant	4/8	ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.423G>A	p.Leu141Leu	synonymous_variant	4/7		NP_057658.2
DRD2	XM_017017296.3	c.423G>A	p.Leu141Leu	synonymous_variant	4/8		XP_016872785.1
DRD2	XM_047426511.1	c.423G>A	p.Leu141Leu	synonymous_variant	4/7		XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.423G>A	p.Leu141Leu	synonymous_variant	4/8	1	NM_000795.4	ENSP00000354859.3

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3559 AN: 152198 Hom.: 66 Cov.: 33

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0292

GnomAD3 exomes AF: 0.0277 AC: 6954 AN: 250762 Hom.: 125 AF XY: 0.0290 AC XY: 3931 AN XY: 135534

Gnomad AFR exome AF: 0.00586

Gnomad AMR exome AF: 0.0139

Gnomad ASJ exome AF: 0.0527

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0316

Gnomad FIN exome AF: 0.0250

Gnomad NFE exome AF: 0.0363

Gnomad OTH exome AF: 0.0380

GnomAD4 exome AF: 0.0353 AC: 51596 AN: 1461740 Hom.: 1023 Cov.: 31 AF XY: 0.0352 AC XY: 25594 AN XY: 727138

Gnomad4 AFR exome AF: 0.00520

Gnomad4 AMR exome AF: 0.0150

Gnomad4 ASJ exome AF: 0.0517

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0325

Gnomad4 FIN exome AF: 0.0255

Gnomad4 NFE exome AF: 0.0387

Gnomad4 OTH exome AF: 0.0342

GnomAD4 genome AF: 0.0234 AC: 3558 AN: 152318 Hom.: 66 Cov.: 33 AF XY: 0.0233 AC XY: 1732 AN XY: 74486

Gnomad4 AFR AF: 0.00705

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0348

Gnomad4 FIN AF: 0.0244

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0336 Hom.: 85

Bravo AF: 0.0218

Asia WGS AF: 0.00982 AC: 34 AN: 3476

EpiCase AF: 0.0351

EpiControl AF: 0.0349

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.1
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1800499; hg19: chr11-113287694;