chr11-113424176-G-A

Variant names:

• chr11-113424176-G-A
• rs2075652
• NM_000795.4:c.285+191C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000795.4(DRD2):​c.285+191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 152,286 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.046 (596 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.224
• Publications: 14 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-113424176-G-A is Benign according to our data. Variant chr11-113424176-G-A is described in ClinVar as Benign. ClinVar VariationId is 1274192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.285+191C>T		intron_variant	Intron 2 of 7	ENST00000362072.8	NP_000786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.285+191C>T		intron_variant	Intron 2 of 7	1	NM_000795.4	ENSP00000354859.3

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6938 AN: 152168 Hom.: 597 Cov.: 33

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00432

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0456 AC: 6943 AN: 152286 Hom.: 596 Cov.: 33 AF XY: 0.0542 AC XY: 4033 AN XY: 74468

African (AFR) AF: 0.0458 AC: 1904 AN: 41562

American (AMR) AF: 0.0707 AC: 1082 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.387 AC: 2003 AN: 5174

South Asian (SAS) AF: 0.0284 AC: 137 AN: 4828

European-Finnish (FIN) AF: 0.131 AC: 1391 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00432 AC: 294 AN: 68018

Other (OTH) AF: 0.0364 AC: 77 AN: 2114

Alfa AF: 0.0142 Hom.: 84

Bravo AF: 0.0430

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.71
PhyloP100		-0.22
PromoterAI		0.0050	Neutral
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: rs2075652; hg19: chr11-113294898;