rs2242041

Positions:

• chr7-50461751-C-G

Variant summary

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

The NM_001082971.2(DDC):​c.*18+1462G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 152,248 control chromosomes in the GnomAD database, including 698 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 0.078 (698 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.*18+1462G>C		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.*18+1462G>C		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11857 AN: 152130 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.0695

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

GnomAD4 genome AF: 0.0779 AC: 11860 AN: 152248 Hom.: 698 Cov.: 32 AF XY: 0.0838 AC XY: 6235 AN XY: 74414

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.0967

Gnomad4 ASJ AF: 0.0545

Gnomad4 EAS AF: 0.0709

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.0914

Gnomad4 OTH AF: 0.0683

Alfa AF: 0.0783 Hom.: 69

Bravo AF: 0.0691

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2242041; hg19: chr7-50529449;