rs1799978

Positions:

• chr11-113475629-T-C

Variant summary

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

The XR_948024.2(LOC105369501):​n.813A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,258 control chromosomes in the GnomAD database, including 836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (836 hom., cov: 32)
  • Exomes 𝑓: 0.047 (0 hom.)
• Consequence: LOC105369501 XR_948024.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.71

Genes affected

LOC105369501 (HGNC:):

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=-0.85).
• BP6: Variant 11-113475629-T-C is Benign according to our data. Variant chr11-113475629-T-C is described in ClinVar as [Benign]. Clinvar id is 225963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105369501	XR_948024.2	n.813A>G		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000540600.5	n.34+29A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13881 AN: 152012 Hom.: 828 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0573

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0762

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.0791

GnomAD4 exome AF: 0.0469 AC: 6 AN: 128 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 5 AN XY: 90

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0185

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.0915 AC: 13916 AN: 152130 Hom.: 836 Cov.: 32 AF XY: 0.0929 AC XY: 6907 AN XY: 74372

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0662

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0763

Gnomad4 FIN AF: 0.0918

Gnomad4 NFE AF: 0.0550

Gnomad4 OTH AF: 0.0797

Alfa AF: 0.0618 Hom.: 427

Bravo AF: 0.0932

Asia WGS AF: 0.109 AC: 382 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1799978; hg19: chr11-113346351;