chr11-113411573-T-G

Position:

• chr11-113411573-T-G

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.1139-653A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,402 control chromosomes in the GnomAD database, including 27,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (27586 hom., cov: 32)
  • Exomes 𝑓: 0.67 (78 hom.)
• Consequence: DRD2 ENST00000362072.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0730

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 11-113411573-T-G is Benign according to our data. Variant chr11-113411573-T-G is described in ClinVar as [Benign]. Clinvar id is 1662326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
DRD2	NM_000795.4	c.1139-653A>C		intron_variant		ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.1052-653A>C		intron_variant			NP_057658.2
DRD2	XM_017017296.3	c.1139-653A>C		intron_variant			XP_016872785.1
DRD2	XM_047426511.1	c.1052-653A>C		intron_variant			XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.1139-653A>C		intron_variant		1	NM_000795.4	ENSP00000354859	P4
	ENST00000546284.1	n.271T>G		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88916 AN: 151966 Hom.: 27586 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.673 AC: 214 AN: 318 Hom.: 78 Cov.: 0 AF XY: 0.735 AC XY: 119 AN XY: 162

Gnomad4 AMR exome AF: 0.643

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.909

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.585 AC: 88935 AN: 152084 Hom.: 27586 Cov.: 32 AF XY: 0.583 AC XY: 43329 AN XY: 74324

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.628

Alfa AF: 0.635 Hom.: 5155

Bravo AF: 0.576

Asia WGS AF: 0.511 AC: 1775 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

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 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.39

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: rs1124493; hg19: chr11-113282295;