11-113412762-G-C

Position:

• chr11-113412762-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000795.4(DRD2):​c.932C>G​(p.Ser311Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0232 in 1,613,788 control chromosomes in the GnomAD database, including 590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (36 hom., cov: 32)
  • Exomes 𝑓: 0.024 (554 hom.)
• Consequence: DRD2 NM_000795.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 5.72

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033855736).
• BP6: Variant 11-113412762-G-C is Benign according to our data. Variant chr11-113412762-G-C is described in ClinVar as [Benign]. Clinvar id is 256813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.932C>G	p.Ser311Cys	missense_variant	7/8	ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.845C>G	p.Ser282Cys	missense_variant	6/7		NP_057658.2
DRD2	XM_017017296.3	c.932C>G	p.Ser311Cys	missense_variant	7/8		XP_016872785.1
DRD2	XM_047426511.1	c.845C>G	p.Ser282Cys	missense_variant	6/7		XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.932C>G	p.Ser311Cys	missense_variant	7/8	1	NM_000795.4	ENSP00000354859	P4

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2886 AN: 152102 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.00439

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0266 AC: 6671 AN: 251194 Hom.: 133 AF XY: 0.0282 AC XY: 3828 AN XY: 135762

Gnomad AFR exome AF: 0.00418

Gnomad AMR exome AF: 0.0213

Gnomad ASJ exome AF: 0.0391

Gnomad EAS exome AF: 0.0354

Gnomad SAS exome AF: 0.0593

Gnomad FIN exome AF: 0.0226

Gnomad NFE exome AF: 0.0206

Gnomad OTH exome AF: 0.0290

GnomAD4 exome AF: 0.0236 AC: 34562 AN: 1461568 Hom.: 554 Cov.: 37 AF XY: 0.0247 AC XY: 17946 AN XY: 727072

Gnomad4 AFR exome AF: 0.00323

Gnomad4 AMR exome AF: 0.0213

Gnomad4 ASJ exome AF: 0.0385

Gnomad4 EAS exome AF: 0.0349

Gnomad4 SAS exome AF: 0.0590

Gnomad4 FIN exome AF: 0.0230

Gnomad4 NFE exome AF: 0.0205

Gnomad4 OTH exome AF: 0.0282

GnomAD4 genome AF: 0.0189 AC: 2883 AN: 152220 Hom.: 36 Cov.: 32 AF XY: 0.0198 AC XY: 1471 AN XY: 74412

Gnomad4 AFR AF: 0.00438

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.0331

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0237 Hom.: 17

Bravo AF: 0.0174

TwinsUK AF: 0.0175 AC: 65

ALSPAC AF: 0.0202 AC: 78

ESP6500AA AF: 0.00636 AC: 28

ESP6500EA AF: 0.0223 AC: 192

ExAC AF: 0.0264 AC: 3203

Asia WGS AF: 0.0650 AC: 224 AN: 3478

EpiCase AF: 0.0245

EpiControl AF: 0.0206

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 29, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	This variant is associated with the following publications: (PMID: 21206399, 11289060, 7907680, 19770837, 18583979, 8824240, 20716857, 25711927, 25504812) -

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	.;T;.;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T;.;T;T;T
MetaRNN	Benign	0.0034	T;T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	.;M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.41	N;N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D;D
Polyphen		0.036	B;D;D;D;.
Vest4		0.32
MPC		1.8
ClinPred		0.019	T
GERP RS		5.7
Varity_R		0.15
gMVP		0.40

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: rs1801028; hg19: chr11-113283484; COSMIC: COSV60758010; COSMIC: COSV60758010;