11-113424520-G-A

Variant names:

• chr11-113424520-G-A
• rs4986918
• NM_000795.4:c.132C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000795.4(DRD2):​c.132C>T​(p.Leu44Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,614,256 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (85 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (77 hom.)
• Consequence: DRD2 NM_000795.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.59
• Publications: 6 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=-0.46).
• BP6: Variant 11-113424520-G-A is Benign according to our data. Variant chr11-113424520-G-A is described in ClinVar as Benign. ClinVar VariationId is 416374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.59 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.132C>T	p.Leu44Leu	synonymous	Exon 2 of 8	NP_000786.1
	DRD2	NM_001440368.1		c.132C>T	p.Leu44Leu	synonymous	Exon 2 of 8	NP_001427297.1
	DRD2	NM_016574.4		c.132C>T	p.Leu44Leu	synonymous	Exon 2 of 7	NP_057658.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.132C>T	p.Leu44Leu	synonymous	Exon 2 of 8	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.132C>T	p.Leu44Leu	synonymous	Exon 1 of 7	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.132C>T	p.Leu44Leu	synonymous	Exon 1 of 7	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2854 AN: 152246 Hom.: 84 Cov.: 33

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00482 AC: 1211 AN: 251454 AF XY: 0.00344

Gnomad AFR exome AF: 0.0656

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00184 AC: 2686 AN: 1461892 Hom.: 77 Cov.: 31 AF XY: 0.00159 AC XY: 1157 AN XY: 727246

African (AFR) AF: 0.0628 AC: 2101 AN: 33480

American (AMR) AF: 0.00344 AC: 154 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.000164 AC: 182 AN: 1112012

Other (OTH) AF: 0.00359 AC: 217 AN: 60396

GnomAD4 genome AF: 0.0187 AC: 2856 AN: 152364 Hom.: 85 Cov.: 33 AF XY: 0.0178 AC XY: 1329 AN XY: 74514

African (AFR) AF: 0.0657 AC: 2731 AN: 41578

American (AMR) AF: 0.00490 AC: 75 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68042

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00965 Hom.: 34

Bravo AF: 0.0206

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.8
DANN	Benign	0.60
PhyloP100		1.6
PromoterAI		-0.024	Neutral
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4986918; hg19: chr11-113295242;