7-50556808-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001082971.2(DDC):c.-29+8477T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,024 control chromosomes in the GnomAD database, including 17,924 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (17924 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.-29+8477T>A		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.-29+8477T>A		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71502 AN: 151906 Hom.: 17902 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.425

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.471 AC: 71567 AN: 152024 Hom.: 17924 Cov.: 32 AF XY: 0.478 AC XY: 35553 AN XY: 74308

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.427

Alfa AF: 0.275 Hom.: 616

Bravo AF: 0.463

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.22
Dann	Benign	0.52

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

Other links and lift over

dbSNP: rs6969081; hg19: chr7-50624505;