rs1110977

Positions:

• chr11-113412643-T-A
• 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>T​(p.Thr351Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,010 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., 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=0.2821554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD2	NM_000795.4	c.1051A>T	p.Thr351Ser	missense_variant	7/8	ENST00000362072.8
DRD2	NM_016574.4	c.964A>T	p.Thr322Ser	missense_variant	6/7
DRD2	XM_017017296.3	c.1051A>T	p.Thr351Ser	missense_variant	7/8
DRD2	XM_047426511.1	c.964A>T	p.Thr322Ser	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.1051A>T	p.Thr351Ser	missense_variant	7/8	1	NM_000795.4	P4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152010 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152010 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74258

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;.;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T;.;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.6	.;L;.;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.25	T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.84	P;P;P;P;.
Vest4		0.36
MutPred		0.42		.;Loss of phosphorylation at T351 (P = 0.1094);.;Loss of phosphorylation at T351 (P = 0.1094);.;
MVP		0.61
MPC		0.78
ClinPred		0.84	D
GERP RS		6.0
Varity_R		0.21
gMVP		0.57

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;