rs2511521

chr11-113414577-G-A

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.724-116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,055,014 control chromosomes in the GnomAD database, including 268,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (30078 hom., cov: 30)
  • Exomes 𝑓: 0.72 (238766 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.659

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=-0.88).
• BP6: Variant 11-113414577-G-A is Benign according to our data. Variant chr11-113414577-G-A is described in ClinVar as [Benign]. Clinvar id is 1263149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD2	NM_000795.4	c.724-116C>T		intron_variant		ENST00000362072.8
DRD2	NM_016574.4	c.723+844C>T		intron_variant
DRD2	XM_017017296.3	c.724-116C>T		intron_variant
DRD2	XM_047426511.1	c.723+844C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.724-116C>T		intron_variant		1	NM_000795.4	P4

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89704 AN: 151662 Hom.: 30075 Cov.: 30

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.654

GnomAD4 exome AF: 0.718 AC: 648075 AN: 903234 Hom.: 238766 AF XY: 0.717 AC XY: 335667 AN XY: 467974

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.698

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.650

Gnomad4 FIN exome AF: 0.703

Gnomad4 NFE exome AF: 0.763

Gnomad4 OTH exome AF: 0.693

GnomAD4 genome AF: 0.591 AC: 89719 AN: 151780 Hom.: 30078 Cov.: 30 AF XY: 0.590 AC XY: 43711 AN XY: 74148

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.652

Alfa AF: 0.669 Hom.: 4548

Bravo AF: 0.580

Asia WGS AF: 0.516 AC: 1796 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.4
Dann	Benign	0.62

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: rs2511521; hg19: chr11-113285299; COSMIC: COSV60764034; COSMIC: COSV60764034;