11-113415768-C-T

Variant names:

• chr11-113415768-C-T
• rs2734839
• NM_000795.4:c.533-157G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000795.4(DRD2):​c.533-157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,974 control chromosomes in the GnomAD database, including 19,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (19144 hom., cov: 32)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.637
• Publications: 29 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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-113415768-C-T is Benign according to our data. Variant chr11-113415768-C-T is described in ClinVar as Benign. ClinVar VariationId is 1249116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.533-157G>A		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.530-157G>A		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.533-157G>A		intron	N/A	NP_057658.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.533-157G>A		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.533-157G>A		intron	N/A	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.530-157G>A		intron	N/A	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72974 AN: 151856 Hom.: 19152 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.533

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.480 AC: 72978 AN: 151974 Hom.: 19144 Cov.: 32 AF XY: 0.469 AC XY: 34800 AN XY: 74252

African (AFR) AF: 0.353 AC: 14614 AN: 41420

American (AMR) AF: 0.406 AC: 6192 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2235 AN: 3466

East Asian (EAS) AF: 0.0585 AC: 302 AN: 5164

South Asian (SAS) AF: 0.364 AC: 1752 AN: 4818

European-Finnish (FIN) AF: 0.476 AC: 5024 AN: 10564

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40928 AN: 67968

Other (OTH) AF: 0.528 AC: 1113 AN: 2106

Alfa AF: 0.397 Hom.: 1196

Bravo AF: 0.471

Asia WGS AF: 0.216 AC: 752 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.67
PhyloP100		-0.64
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: rs2734839; hg19: chr11-113286490;