rs1817074

Positions:

• chr7-50506314-T-C

Variant summary

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

The NM_001082971.2(DDC):​c.715-2255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,900 control chromosomes in the GnomAD database, including 10,715 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 0.37 (10715 hom., cov: 31)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.715-2255A>G		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.715-2255A>G		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56269 AN: 151782 Hom.: 10693 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.371 AC: 56335 AN: 151900 Hom.: 10715 Cov.: 31 AF XY: 0.378 AC XY: 28051 AN XY: 74244

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.357

Alfa AF: 0.363 Hom.: 1245

Bravo AF: 0.372

Asia WGS AF: 0.264 AC: 919 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	0.99
DANN	Benign	0.23

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: rs1817074; hg19: chr7-50574012;