chr11-113412766-G-C

Variant names:

• chr11-113412766-G-C
• rs1800496
• NM_000795.4:c.928C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000795.4(DRD2):​c.928C>G​(p.Pro310Ala) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P310S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRD2 NM_000795.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08279839).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.928C>G	p.Pro310Ala	missense	Exon 7 of 8	NP_000786.1
	DRD2	NM_001440368.1		c.925C>G	p.Pro309Ala	missense	Exon 7 of 8	NP_001427297.1
	DRD2	NM_016574.4		c.841C>G	p.Pro281Ala	missense	Exon 6 of 7	NP_057658.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.928C>G	p.Pro310Ala	missense	Exon 7 of 8	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.928C>G	p.Pro310Ala	missense	Exon 6 of 7	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.925C>G	p.Pro309Ala	missense	Exon 6 of 7	ENSP00000441068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.73
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.77	N
PhyloP100		0.41
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.063
Sift	Benign	0.46	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.29		Loss of catalytic residue at P310 (P = 0.053)
MVP		0.65
MPC		0.79
ClinPred		0.52	D
GERP RS		1.6
Varity_R		0.027
gMVP		0.22
Mutation Taster		=92/8	polymorphism

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: rs1800496; hg19: chr11-113283488;