Variant 7-50529166-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001082971.2(DDC):c.570+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,610,546 control chromosomes in the GnomAD database, including 49,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5918 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43341 hom. )

Consequence

DDC
NM_001082971.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.48

Variant links:

Genes affected

DDC (HGNC:2719): (dopa decarboxylase) The encoded protein catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine. Defects in this gene are the cause of aromatic L-amino-acid decarboxylase deficiency (AADCD). AADCD deficiency is an inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2011]

DDC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-50529166-C-T is Benign according to our data. Variant chr7-50529166-C-T is described in ClinVar as [Benign]. Clinvar id is 1256784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2 link	c.570+42G>A		intron_variant		ENST00000444124.7	NP_001076440.2	P20711-1Q53Y41A0A0S2Z3N4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7 link	c.570+42G>A		intron_variant		1	NM_001082971.2	ENSP00000403644.2		P20711-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40997

AN:

151902

Hom.:

5907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.358

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.246

AC:

61918

AN:

251274

Hom.:

8413

AF XY:

0.252

AC XY:

34201

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.363

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.404

Gnomad SAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.239

AC:

349002

AN:

1458528

Hom.:

43341

Cov.:

AF XY:

0.242

AC XY:

175589

AN XY:

725654

show subpopulations

Gnomad4 AFR exome

AF:

0.363

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.197

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.270

AC:

41032

AN:

152018

Hom.:

5918

Cov.:

AF XY:

0.268

AC XY:

19915

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.358

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.396

Gnomad4 SAS

AF:

0.322

Gnomad4 FIN

AF:

0.209

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.256

Hom.:

1583

Bravo

AF:

0.271

Asia WGS

AF:

0.333

AC:

1158

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 26, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.72

DANN

Benign

0.51

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