11-113458088-G-C

Variant names:

• chr11-113458088-G-C
• rs74751335
• NM_000795.4:c.-32+16988C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000795.4(DRD2):​c.-32+16988C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,324 control chromosomes in the GnomAD database, including 461 homozygotes. 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 0.073 (461 hom., cov: 34)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.-32+16988C>G		intron_variant	Intron 1 of 7	ENST00000362072.8	NP_000786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.-32+16988C>G		intron_variant	Intron 1 of 7	1	NM_000795.4	ENSP00000354859.3
DRD2	ENST00000346454.7	c.-32+16988C>G		intron_variant	Intron 1 of 6	1		ENSP00000278597.5
DRD2	ENST00000540600.5	n.34+17570C>G		intron_variant	Intron 1 of 5	1
DRD2	ENST00000542616.1	c.-32+16142C>G		intron_variant	Intron 2 of 2	4		ENSP00000441474.1

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11158 AN: 152206 Hom.: 460 Cov.: 34

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0587

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.0650

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0734 AC: 11177 AN: 152324 Hom.: 461 Cov.: 34 AF XY: 0.0750 AC XY: 5584 AN XY: 74486

African (AFR) AF: 0.0955 AC: 3968 AN: 41570

American (AMR) AF: 0.0587 AC: 898 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.144 AC: 746 AN: 5180

South Asian (SAS) AF: 0.0729 AC: 352 AN: 4830

European-Finnish (FIN) AF: 0.0924 AC: 981 AN: 10618

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0549 AC: 3738 AN: 68030

Other (OTH) AF: 0.0658 AC: 139 AN: 2114

Alfa AF: 0.0701 Hom.: 39

Bravo AF: 0.0721

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.1
DANN	Benign	0.80
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs74751335; hg19: chr11-113328810;