rs1800499

Variant names:

• chr11-113416972-C-T
• rs1800499
• NM_000795.4:c.423G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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 -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 Benign/Likely_benign. ClinVar VariationId is 238185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3558 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.423G>A	p.Leu141Leu	synonymous_variant	Exon 4 of 8	ENST00000362072.8	NP_000786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.423G>A	p.Leu141Leu	synonymous_variant	Exon 4 of 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

GnomAD2 exomes AF: 0.0277 AC: 6954 AN: 250762 AF XY: 0.0290

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 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

African (AFR) AF: 0.00520 AC: 174 AN: 33476

American (AMR) AF: 0.0150 AC: 669 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0517 AC: 1350 AN: 26124

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0325 AC: 2801 AN: 86212

European-Finnish (FIN) AF: 0.0255 AC: 1362 AN: 53408

Middle Eastern (MID) AF: 0.0314 AC: 181 AN: 5768

European-Non Finnish (NFE) AF: 0.0387 AC: 42990 AN: 1111946

Other (OTH) AF: 0.0342 AC: 2067 AN: 60390

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

African (AFR) AF: 0.00705 AC: 293 AN: 41568

American (AMR) AF: 0.0157 AC: 240 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0348 AC: 168 AN: 4822

European-Finnish (FIN) AF: 0.0244 AC: 259 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0346 AC: 2354 AN: 68032

Other (OTH) AF: 0.0289 AC: 61 AN: 2112

Alfa AF: 0.0332 Hom.: 201

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

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dystonic disorder Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.1
DANN	Benign	0.80
PhyloP100		0.11
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800499; hg19: chr11-113287694;