11-113412643-T-C

Position:

• chr11-113412643-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.1051A>G	p.Thr351Ala	missense_variant	7/8	ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.964A>G	p.Thr322Ala	missense_variant	6/7		NP_057658.2
DRD2	XM_017017296.3	c.1051A>G	p.Thr351Ala	missense_variant	7/8		XP_016872785.1
DRD2	XM_047426511.1	c.964A>G	p.Thr322Ala	missense_variant	6/7		XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.1051A>G	p.Thr351Ala	missense_variant	7/8	1	NM_000795.4	ENSP00000354859.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T;.;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.9	.;L;.;L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.33	T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.68	P;P;P;P;.
Vest4		0.38
MutPred		0.44		.;Loss of phosphorylation at T351 (P = 0.0115);.;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

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: rs1110977; hg19: chr11-113283365;