Genetic Variant NM_000795.4:c.1138+65T>G (chr11-113412491-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000795.4(DRD2):c.1138+65T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 1,578,046 control chromosomes in the GnomAD database, including 922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 499 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 423 hom. )

Consequence

DRD2
NM_000795.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.615

Publications

3 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-113412491-A-C is Benign according to our data. Variant chr11-113412491-A-C is described in ClinVar as [Benign]. Clinvar id is 1253502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD2	NM_000795.4 link	c.1138+65T>G		intron_variant	Intron 7 of 7	ENST00000362072.8	NP_000786.1	P14416-1A0A024R3C5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD2	ENST00000362072.8 link	c.1138+65T>G		intron_variant	Intron 7 of 7	1	NM_000795.4	ENSP00000354859.3		P14416-1

Frequencies

GnomAD3 genomes

AF:

0.0437

AC:

6645

AN:

152162

Hom.:

499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0320

GnomAD4 exome

AF:

0.00444

AC:

6326

AN:

1425766

Hom.:

423

AF XY:

0.00381

AC XY:

2705

AN XY:

710506

show subpopulations

African (AFR)

AF:

0.154

AC:

5083

AN:

32912

American (AMR)

AF:

0.00797

AC:

351

AN:

44024

Ashkenazi Jewish (ASJ)

AF:

0.00132

AC:

AN:

25800

East Asian (EAS)

AF:

0.00

AC:

AN:

39480

South Asian (SAS)

AF:

0.000497

AC:

AN:

84468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44250

Middle Eastern (MID)

AF:

0.00648

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.000204

AC:

222

AN:

1089674

Other (OTH)

AF:

0.00937

AC:

557

AN:

59446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

319

638

958

1277

1596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0437

AC:

6654

AN:

152280

Hom.:

499

Cov.:

AF XY:

0.0418

AC XY:

3115

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.152

AC:

6331

AN:

41530

American (AMR)

AF:

0.0137

AC:

209

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68030

Other (OTH)

AF:

0.0317

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

301

601

902

1202

1503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0156

Hom.:

Bravo

AF:

0.0495

Asia WGS

AF:

0.00982

AC:

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 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

-0.80

CADD

Benign

3.7

(source)

DANN

Benign

0.65

PhyloP100

0.61

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_000795.4:c.1138+65T>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over