rs6277

Positions:

• chr11-113412737-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000795.4(DRD2):​c.957C>T​(p.Pro319=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,613,936 control chromosomes in the GnomAD database, including 206,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (13521 hom., cov: 32)
  • Exomes 𝑓: 0.50 (192984 hom.)
• Consequence: DRD2 NM_000795.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.127

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-113412737-G-A is Benign according to our data. Variant chr11-113412737-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 198436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.127 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.957C>T	p.Pro319=	synonymous_variant	7/8	ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.870C>T	p.Pro290=	synonymous_variant	6/7		NP_057658.2
DRD2	XM_017017296.3	c.957C>T	p.Pro319=	synonymous_variant	7/8		XP_016872785.1
DRD2	XM_047426511.1	c.870C>T	p.Pro290=	synonymous_variant	6/7		XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.957C>T	p.Pro319=	synonymous_variant	7/8	1	NM_000795.4	ENSP00000354859	P4

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57167 AN: 151962 Hom.: 13534 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.0597

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.432

GnomAD3 exomes AF: 0.411 AC: 103247 AN: 251142 Hom.: 24917 AF XY: 0.426 AC XY: 57805 AN XY: 135740

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.542

Gnomad EAS exome AF: 0.0568

Gnomad SAS exome AF: 0.379

Gnomad FIN exome AF: 0.458

Gnomad NFE exome AF: 0.543

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.499 AC: 730118 AN: 1461856 Hom.: 192984 Cov.: 93 AF XY: 0.498 AC XY: 362363 AN XY: 727230

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.0605

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.376 AC: 57143 AN: 152080 Hom.: 13521 Cov.: 32 AF XY: 0.368 AC XY: 27371 AN XY: 74356

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.429

Alfa AF: 0.471 Hom.: 10466

Bravo AF: 0.358

Asia WGS AF: 0.193 AC: 674 AN: 3478

EpiCase AF: 0.553

EpiControl AF: 0.561

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 09, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.79
DANN	Benign	0.75

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: rs6277; hg19: chr11-113283459; COSMIC: COSV60757274; COSMIC: COSV60757274;