dbSNP rs2511521: DRD2:c.724-116C>T (chr11-113414577-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000795.4(DRD2):c.724-116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,055,014 control chromosomes in the GnomAD database, including 268,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 30078 hom., cov: 30)

Exomes 𝑓: 0.72 ( 238766 hom. )

Consequence

DRD2
NM_000795.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.659

Variant links:

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]

DRD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-113414577-G-A is Benign according to our data. Variant chr11-113414577-G-A is described in ClinVar as [Benign]. Clinvar id is 1263149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4 link	c.724-116C>T	intron_variant	Intron 5 of 7	ENST00000362072.8	NP_000786.1	P14416-1A0A024R3C5
DRD2	NM_016574.4 link	c.723+844C>T	intron_variant	Intron 5 of 6		NP_057658.2	P14416-2A0A024R3I6
DRD2	XM_017017296.3 link	c.724-116C>T	intron_variant	Intron 5 of 7		XP_016872785.1	P14416-1A0A024R3C5
DRD2	XM_047426511.1 link	c.723+844C>T	intron_variant	Intron 5 of 6		XP_047282467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8 link	c.724-116C>T		intron_variant	Intron 5 of 7	1	NM_000795.4	ENSP00000354859.3		P14416-1

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89704

AN:

151662

Hom.:

30075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.807

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.751

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.758

Gnomad OTH

AF:

0.654

GnomAD4 exome

AF:

0.718

AC:

648075

AN:

903234

Hom.:

238766

AF XY:

0.717

AC XY:

335667

AN XY:

467974

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.698

Gnomad4 ASJ exome

AF:

0.750

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.650

Gnomad4 FIN exome

AF:

0.703

Gnomad4 NFE exome

AF:

0.763

Gnomad4 OTH exome

AF:

0.693

GnomAD4 genome

AF:

0.591

AC:

89719

AN:

151780

Hom.:

30078

Cov.:

AF XY:

0.590

AC XY:

43711

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.257

Gnomad4 AMR

AF:

0.657

Gnomad4 ASJ

AF:

0.751

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.630

Gnomad4 FIN

AF:

0.689

Gnomad4 NFE

AF:

0.758

Gnomad4 OTH

AF:

0.652

Alfa

AF:

0.669

Hom.:

4548

Bravo

AF:

0.580

Asia WGS

AF:

0.516

AC:

1796

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.4

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over