rs1076560

Positions:

• chr11-113412966-C-A
• chr11-113412966-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000795.4(DRD2):​c.811-83G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,458,296 control chromosomes in the GnomAD database, including 25,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2565 hom., cov: 32)
  • Exomes 𝑓: 0.18 (22891 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.298

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-113412966-C-A is Benign according to our data. Variant chr11-113412966-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 375655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.811-83G>T		intron_variant		ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.724-83G>T		intron_variant			NP_057658.2
DRD2	XM_017017296.3	c.811-83G>T		intron_variant			XP_016872785.1
DRD2	XM_047426511.1	c.724-83G>T		intron_variant			XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.811-83G>T		intron_variant		1	NM_000795.4	ENSP00000354859	P4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25135 AN: 151954 Hom.: 2556 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.175 AC: 228600 AN: 1306224 Hom.: 22891 AF XY: 0.177 AC XY: 114338 AN XY: 647428

Gnomad4 AFR exome AF: 0.0838

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.165 AC: 25163 AN: 152072 Hom.: 2565 Cov.: 32 AF XY: 0.173 AC XY: 12842 AN XY: 74328

Gnomad4 AFR AF: 0.0892

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.167

Alfa AF: 0.149 Hom.: 1496

Bravo AF: 0.170

Asia WGS AF: 0.317 AC: 1101 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	This variant is associated with the following publications: (PMID: 17196743, 22569179, 18077373, 21150907, 26347318, 19940176, 18829695) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1076560; hg19: chr11-113283688;