rs6279

Positions:

• chr11-113410351-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000795.4(DRD2):​c.*376C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 426,798 control chromosomes in the GnomAD database, including 87,374 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (27551 hom., cov: 32)
  • Exomes 𝑓: 0.65 (59823 hom.)
• Consequence: DRD2 NM_000795.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• 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.*376C>G		3_prime_UTR_variant	8/8	ENST00000362072.8	NP_000786.1
DRD2	NM_016574.4	c.*376C>G		3_prime_UTR_variant	7/7		NP_057658.2
DRD2	XM_017017296.3	c.*376C>G		3_prime_UTR_variant	8/8		XP_016872785.1
DRD2	XM_047426511.1	c.*376C>G		3_prime_UTR_variant	7/7		XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.*376C>G		3_prime_UTR_variant	8/8	1	NM_000795.4	ENSP00000354859	P4
	ENST00000546284.1	n.245-1196G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88822 AN: 151908 Hom.: 27551 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.652 AC: 179165 AN: 274772 Hom.: 59823 Cov.: 0 AF XY: 0.651 AC XY: 94070 AN XY: 144540

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.653

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.433

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.671

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.645

GnomAD4 genome AF: 0.584 AC: 88842 AN: 152026 Hom.: 27551 Cov.: 32 AF XY: 0.583 AC XY: 43299 AN XY: 74306

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.627

Alfa AF: 0.644 Hom.: 4053

Bravo AF: 0.576

Asia WGS AF: 0.512 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.66

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: rs6279; hg19: chr11-113281073;