NM_000795.4:c.1051A>G

Variant names:

• chr11-113412643-T-C
• rs1110977
• NM_000795.4:c.1051A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000795.4(DRD2):​c.1051A>G​(p.Thr351Ala) variant causes a missense change. 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DRD2 NM_000795.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.13
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27659932).

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.1051A>G	p.Thr351Ala	missense	Exon 7 of 8	NP_000786.1
	DRD2	NM_001440368.1		c.1048A>G	p.Thr350Ala	missense	Exon 7 of 8	NP_001427297.1
	DRD2	NM_016574.4		c.964A>G	p.Thr322Ala	missense	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.1051A>G	p.Thr351Ala	missense	Exon 7 of 8	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.1051A>G	p.Thr351Ala	missense	Exon 6 of 7	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.1048A>G	p.Thr350Ala	missense	Exon 6 of 7	ENSP00000441068.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.28
Sift	Benign	0.33	T
Sift4G	Benign	0.30	T
Polyphen		0.68	P
Vest4		0.38
MutPred		0.44		Loss of phosphorylation at T351 (P = 0.0115)
MVP		0.62
MPC		0.89
ClinPred		0.71	D
GERP RS		6.0
Varity_R		0.23
gMVP		0.73
Mutation Taster		=27/73	disease causing

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: rs1110977; hg19: chr11-113283365;