rs998850

Positions:

• chr7-50539690-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001082971.2(DDC):​c.315+225C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 534,666 control chromosomes in the GnomAD database, including 60,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15231 hom., cov: 32)
  • Exomes 𝑓: 0.48 (45143 hom.)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0140

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-50539690-G-C is Benign according to our data. Variant chr7-50539690-G-C is described in ClinVar as [Benign]. Clinvar id is 1245436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2	c.315+225C>G		intron_variant		ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.315+225C>G		intron_variant		1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66094 AN: 151922 Hom.: 15219 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.478 AC: 182929 AN: 382626 Hom.: 45143 AF XY: 0.472 AC XY: 96027 AN XY: 203466

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome AF: 0.435 AC: 66122 AN: 152040 Hom.: 15231 Cov.: 32 AF XY: 0.426 AC XY: 31662 AN XY: 74316

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.468

Alfa AF: 0.471 Hom.: 2133

Bravo AF: 0.430

Asia WGS AF: 0.422 AC: 1472 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 54% 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: 50. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs998850; hg19: chr7-50607388;