rs12363125

Positions:

• chr11-113415194-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000795.4(DRD2):​c.723+227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 431,872 control chromosomes in the GnomAD database, including 59,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (16970 hom., cov: 32)
  • Exomes 𝑓: 0.52 (42152 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0550

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-113415194-C-T is Benign according to our data. Variant chr11-113415194-C-T is described in ClinVar as [Benign]. Clinvar id is 1272787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.723+227G>A		intron_variant		ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.723+227G>A		intron_variant			NP_057658.2
DRD2	XM_017017296.3	c.723+227G>A		intron_variant			XP_016872785.1
DRD2	XM_047426511.1	c.723+227G>A		intron_variant			XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.723+227G>A		intron_variant		1	NM_000795.4	ENSP00000354859.3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64883 AN: 151750 Hom.: 16982 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.520 AC: 145529 AN: 280004 Hom.: 42152 AF XY: 0.523 AC XY: 74295 AN XY: 141952

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.645

Gnomad4 EAS exome AF: 0.0603

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.602

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.427 AC: 64871 AN: 151868 Hom.: 16970 Cov.: 32 AF XY: 0.417 AC XY: 30969 AN XY: 74214

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.0581

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.491

Alfa AF: 0.563 Hom.: 30276

Bravo AF: 0.412

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12363125; hg19: chr11-113285916;