Variant 11-637536-GCCGCCGACCTCCT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000797.4(DRD4):c.235_247del(p.Ala79SerfsTer21) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,564,018 control chromosomes in the GnomAD database, including 170 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A78A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.010 ( 17 hom., cov: 32)

Exomes 𝑓: 0.013 ( 153 hom. )

Consequence

DRD4
NM_000797.4 frameshift

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided P:1B:2

Conservation

PhyloP100: 7.73

Variant links:

Genes affected

DRD4 (HGNC:3025): (dopamine receptor D4) This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, and the personality trait of novelty seeking. This gene contains a polymorphic number (2-10 copies) of tandem 48 nt repeats; the sequence shown contains four repeats. [provided by RefSeq, Jul 2008]

DRD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 1545 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD4	NM_000797.4 linkuse as main transcript	c.235_247del	p.Ala79SerfsTer21	frameshift_variant	1/4	ENST00000176183.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD4	ENST00000176183.6 linkuse as main transcript	c.235_247del	p.Ala79SerfsTer21	frameshift_variant	1/4	1	NM_000797.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1545

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0411

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00771

AC:

1319

AN:

171114

Hom.:

AF XY:

0.00756

AC XY:

701

AN XY:

92706

show subpopulations

Gnomad AFR exome

AF:

0.000770

Gnomad AMR exome

AF:

0.00167

Gnomad ASJ exome

AF:

0.00503

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000207

Gnomad FIN exome

AF:

0.0279

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.00935

GnomAD4 exome

AF:

0.0126

AC:

17828

AN:

1411754

Hom.:

153

AF XY:

0.0123

AC XY:

8616

AN XY:

698834

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00173

Gnomad4 ASJ exome

AF:

0.00595

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000248

Gnomad4 FIN exome

AF:

0.0365

Gnomad4 NFE exome

AF:

0.0142

Gnomad4 OTH exome

AF:

0.00971

GnomAD4 genome

AF:

0.0101

AC:

1545

AN:

152264

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

809

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0411

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.00736

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autonomic nervous system dysfunction

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 1994

- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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