rs6276

Variant names:

• chr11-113410675-C-T
• rs6276
• NM_000795.4:c.*52G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000795.4(DRD2):​c.*52G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 1,610,646 control chromosomes in the GnomAD database, including 364,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (25559 hom., cov: 33)
  • Exomes 𝑓: 0.68 (339111 hom.)
• Consequence: DRD2 NM_000795.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.409
• Publications: 75 publications found

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]

ENSG00000256757 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-113410675-C-T is Benign according to our data. Variant chr11-113410675-C-T is described in ClinVar as [Benign]. Clinvar id is 1277750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4	c.*52G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000362072.8	NP_000786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8	c.*52G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_000795.4	ENSP00000354859.3

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82256 AN: 151940 Hom.: 25557 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.609

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.675 AC: 984876 AN: 1458588 Hom.: 339111 Cov.: 34 AF XY: 0.675 AC XY: 489888 AN XY: 725750

African (AFR) AF: 0.191 AC: 6396 AN: 33400

American (AMR) AF: 0.662 AC: 29581 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 16909 AN: 26122

East Asian (EAS) AF: 0.445 AC: 17655 AN: 39678

South Asian (SAS) AF: 0.622 AC: 53561 AN: 86064

European-Finnish (FIN) AF: 0.666 AC: 35502 AN: 53302

Middle Eastern (MID) AF: 0.591 AC: 3030 AN: 5126

European-Non Finnish (NFE) AF: 0.706 AC: 783431 AN: 1109966

Other (OTH) AF: 0.644 AC: 38811 AN: 60224

GnomAD4 genome AF: 0.541 AC: 82267 AN: 152058 Hom.: 25559 Cov.: 33 AF XY: 0.541 AC XY: 40214 AN XY: 74310

African (AFR) AF: 0.218 AC: 9031 AN: 41466

American (AMR) AF: 0.602 AC: 9200 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2268 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2365 AN: 5160

South Asian (SAS) AF: 0.601 AC: 2895 AN: 4814

European-Finnish (FIN) AF: 0.658 AC: 6967 AN: 10590

Middle Eastern (MID) AF: 0.590 AC: 171 AN: 290

European-Non Finnish (NFE) AF: 0.698 AC: 47461 AN: 67954

Other (OTH) AF: 0.597 AC: 1263 AN: 2114

Alfa AF: 0.593 Hom.: 10414

Bravo AF: 0.527

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.85
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6276; hg19: chr11-113281397; COSMIC: COSV60759265; COSMIC: COSV60759265;