rs71653614

Positions:

• chr11-113412715-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_000795.4(DRD2):​c.979A>G​(p.Lys327Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,614,202 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (22 hom.)
• Consequence: DRD2 NM_000795.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.02

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 -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, DRD2
• BP4: Computational evidence support a benign effect (MetaRNN=0.006436944).
• BP6: Variant 11-113412715-T-C is Benign according to our data. Variant chr11-113412715-T-C is described in ClinVar as [Benign]. Clinvar id is 238186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 541 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD2	NM_000795.4	c.979A>G	p.Lys327Glu	missense_variant	7/8	ENST00000362072.8
DRD2	NM_016574.4	c.892A>G	p.Lys298Glu	missense_variant	6/7
DRD2	XM_017017296.3	c.979A>G	p.Lys327Glu	missense_variant	7/8
DRD2	XM_047426511.1	c.892A>G	p.Lys298Glu	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.979A>G	p.Lys327Glu	missense_variant	7/8	1	NM_000795.4	P4

Frequencies

GnomAD3 genomes AF: 0.00354 AC: 539 AN: 152192 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00389

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00378 AC: 949 AN: 251342 Hom.: 11 AF XY: 0.00386 AC XY: 524 AN XY: 135850

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00261

Gnomad FIN exome AF: 0.0205

Gnomad NFE exome AF: 0.00325

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00307 AC: 4491 AN: 1461892 Hom.: 22 Cov.: 31 AF XY: 0.00312 AC XY: 2267 AN XY: 727248

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00227

Gnomad4 FIN exome AF: 0.0207

Gnomad4 NFE exome AF: 0.00267

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.00355 AC: 541 AN: 152310 Hom.: 3 Cov.: 33 AF XY: 0.00427 AC XY: 318 AN XY: 74464

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0205

Gnomad4 NFE AF: 0.00389

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00261 Hom.: 1

Bravo AF: 0.00151

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.00349 AC: 30

ExAC AF: 0.00381 AC: 463

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00251

EpiControl AF: 0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	-0.0048
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	D;.;D;D;D
MetaRNN	Benign	0.0064	T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.57	N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.31	T;T;T;T;T
Sift4G	Benign	0.71	T;T;T;T;T
Polyphen		0.0070	B;B;B;B;.
Vest4		0.49
MVP		0.84
MPC		1.3
ClinPred		0.050	T
GERP RS		6.0
Varity_R		0.30
gMVP		0.48

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: rs71653614; hg19: chr11-113283437;