11-113412491-A-C

Position:

• chr11-113412491-A-C

Variant summary

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

The ENST00000362072.8(DRD2):​c.1138+65T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 1,578,046 control chromosomes in the GnomAD database, including 922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (499 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (423 hom.)
• Consequence: DRD2 ENST00000362072.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.615

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=-0.8).
• BP6: Variant 11-113412491-A-C is Benign according to our data. Variant chr11-113412491-A-C is described in ClinVar as [Benign]. Clinvar id is 1253502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD2	NM_000795.4	c.1138+65T>G		intron_variant		ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.1051+65T>G		intron_variant			NP_057658.2
DRD2	XM_017017296.3	c.1138+65T>G		intron_variant			XP_016872785.1
DRD2	XM_047426511.1	c.1051+65T>G		intron_variant			XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.1138+65T>G		intron_variant		1	NM_000795.4	ENSP00000354859	P4

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6645 AN: 152162 Hom.: 499 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.00444 AC: 6326 AN: 1425766 Hom.: 423 AF XY: 0.00381 AC XY: 2705 AN XY: 710506

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.00797

Gnomad4 ASJ exome AF: 0.00132

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000497

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000204

Gnomad4 OTH exome AF: 0.00937

GnomAD4 genome AF: 0.0437 AC: 6654 AN: 152280 Hom.: 499 Cov.: 33 AF XY: 0.0418 AC XY: 3115 AN XY: 74474

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.00832 Hom.: 12

Bravo AF: 0.0495

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.7
DANN	Benign	0.65

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: rs57666437; hg19: chr11-113283213;