chr11-113412737-G-C

Variant names:

• chr11-113412737-G-C
• rs6277
• NM_000795.4:c.957C>G
• DRD2 p.Pro319Pro

Variant summary

Our verdict is

Likely benign

-3 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000795.4(DRD2):​c.957C>G​(p.Pro319Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P319P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRD2 NM_000795.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 0 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]

DRD2 Gene-Disease associations (from GenCC):

• combined dystonia

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.127 with no splicing effect.

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.957C>G	p.Pro319Pro	synonymous	Exon 7 of 8	NP_000786.1	P14416-1
	DRD2	NM_001440368.1		c.954C>G	p.Pro318Pro	synonymous	Exon 7 of 8	NP_001427297.1
	DRD2	NM_016574.4		c.870C>G	p.Pro290Pro	synonymous	Exon 6 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.957C>G	p.Pro319Pro	synonymous	Exon 7 of 8	ENSP00000354859.3	P14416-1
	DRD2	ENST00000542968.5	TSL:1	c.957C>G	p.Pro319Pro	synonymous	Exon 6 of 7	ENSP00000442172.1	P14416-1
	DRD2	ENST00000544518.5	TSL:1	c.954C>G	p.Pro318Pro	synonymous	Exon 6 of 7	ENSP00000441068.1	F8VUV1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 93

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.23
DANN	Benign	0.61
PhyloP100		-0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6277;

hg19: chr11-113283459;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline