11-113411054-A-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.1139-134T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 916,124 control chromosomes in the GnomAD database, including 206,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (28591 hom., cov: 31)
  • Exomes 𝑓: 0.68 (177447 hom.)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.27

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-113411054-A-C is Benign according to our data. Variant chr11-113411054-A-C is described in ClinVar as [Benign]. Clinvar id is 1238634.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD2	NM_000795.4	c.1139-134T>G		intron_variant		ENST00000362072.8
DRD2	NM_016574.4	c.1052-134T>G		intron_variant
DRD2	XM_017017296.3	c.1139-134T>G		intron_variant
DRD2	XM_047426511.1	c.1052-134T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD2	ENST00000362072.8	c.1139-134T>G		intron_variant		1	NM_000795.4	P4
	ENST00000546284.1	n.245-493A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91332 AN: 151762 Hom.: 28585 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.639

GnomAD4 exome AF: 0.676 AC: 516362 AN: 764244 Hom.: 177447 AF XY: 0.675 AC XY: 260853 AN XY: 386402

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.655

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.440

Gnomad4 SAS exome AF: 0.646

Gnomad4 FIN exome AF: 0.668

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.655

GnomAD4 genome AF: 0.602 AC: 91365 AN: 151880 Hom.: 28591 Cov.: 31 AF XY: 0.599 AC XY: 44508 AN XY: 74254

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.636

Alfa AF: 0.553 Hom.: 1692

Bravo AF: 0.595

Asia WGS AF: 0.531 AC: 1848 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	-0.96
Cadd	Benign	0.0020
Dann	Benign	0.58

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: rs2734841; hg19: chr11-113281776;