11-113418460-T-C

Variant names:

• chr11-113418460-T-C
• rs1079727
• NM_000795.4:c.286-324A>G

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.286-324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,190 control chromosomes in the GnomAD database, including 2,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2543 hom., cov: 33)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0480
• Publications: 29 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=-0.91).
• BP6: Variant 11-113418460-T-C is Benign according to our data. Variant chr11-113418460-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271634.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.286-324A>G		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.290-331A>G		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.286-324A>G		intron	N/A	NP_057658.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.286-324A>G		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.286-324A>G		intron	N/A	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.290-331A>G		intron	N/A	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24862 AN: 152072 Hom.: 2534 Cov.: 33

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.164 AC: 24889 AN: 152190 Hom.: 2543 Cov.: 33 AF XY: 0.172 AC XY: 12761 AN XY: 74388

African (AFR) AF: 0.0890 AC: 3694 AN: 41516

American (AMR) AF: 0.267 AC: 4082 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2152 AN: 5180

South Asian (SAS) AF: 0.265 AC: 1275 AN: 4820

European-Finnish (FIN) AF: 0.211 AC: 2232 AN: 10582

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10631 AN: 68014

Other (OTH) AF: 0.160 AC: 339 AN: 2116

Alfa AF: 0.161 Hom.: 1345

Bravo AF: 0.167

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.67
PhyloP100		0.048
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: rs1079727; hg19: chr11-113289182;