rs4490786

Positions:

chr7-50476616-C-T

Variant summary

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

The NM_001082971.2(DDC):c.1041+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,608,232 control chromosomes in the GnomAD database, including 36,358 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3562 hom., cov: 32)

Exomes 𝑓: 0.21 ( 32796 hom. )

Consequence

DDC
NM_001082971.2 splice_region, intron

Scores

Splicing: ADA: 0.00003647

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.166

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=-0.81).

BP6

Variant 7-50476616-C-T is Benign according to our data. Variant chr7-50476616-C-T is described in ClinVar as [Benign]. Clinvar id is 360432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-50476616-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2 linkuse as main transcript	c.1041+8G>A		splice_region_variant, intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7 linkuse as main transcript	c.1041+8G>A		splice_region_variant, intron_variant		1	NM_001082971.2	P1	P20711-1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32317

AN:

151990

Hom.:

3558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.198

GnomAD3 exomes

AF:

0.209

AC:

52149

AN:

249656

Hom.:

5661

AF XY:

0.208

AC XY:

28071

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.241

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.210

AC:

306046

AN:

1456124

Hom.:

32796

Cov.:

AF XY:

0.210

AC XY:

151883

AN XY:

724660

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.243

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.213

AC:

32328

AN:

152108

Hom.:

3562

Cov.:

AF XY:

0.216

AC XY:

16077

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.223

Gnomad4 AMR

AF:

0.212

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.203

Hom.:

3906

Bravo

AF:

0.211

Asia WGS

AF:

0.142

AC:

495

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.194

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of aromatic-L-amino-acid decarboxylase

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 04, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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 41% 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: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.3

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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