rs12808482

chr11-113424276-T-Achr11-113424276-T-C

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.285+91A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,430,594 control chromosomes in the GnomAD database, including 226,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (17499 hom., cov: 32)
  • Exomes 𝑓: 0.56 (208553 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0810

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 11-113424276-T-A is Benign according to our data. Variant chr11-113424276-T-A is described in ClinVar as [Benign]. Clinvar id is 1289649.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD2	NM_000795.4	c.285+91A>T		intron_variant		ENST00000362072.8
DRD2	NM_016574.4	c.285+91A>T		intron_variant
DRD2	XM_017017296.3	c.285+91A>T		intron_variant
DRD2	XM_047426511.1	c.285+91A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.285+91A>T		intron_variant		1	NM_000795.4	P4

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67383 AN: 151886 Hom.: 17510 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.557 AC: 711755 AN: 1278590 Hom.: 208553 AF XY: 0.554 AC XY: 351763 AN XY: 635468

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.652

Gnomad4 EAS exome AF: 0.0604

Gnomad4 SAS exome AF: 0.401

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.533

GnomAD4 genome AF: 0.443 AC: 67379 AN: 152004 Hom.: 17499 Cov.: 32 AF XY: 0.433 AC XY: 32162 AN XY: 74296

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.501

Alfa AF: 0.376 Hom.: 1126

Bravo AF: 0.431

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.40

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: rs12808482; hg19: chr11-113294998;