rs880028

Variant names:

• chr7-50502438-A-G
• rs880028
• NM_001082971.2:c.781+1555T>C

Variant summary

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

The NM_001082971.2(DDC):​c.781+1555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,088 control chromosomes in the GnomAD database, including 3,528 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 0.21 (3528 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.781+1555T>C		intron_variant	Intron 7 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.781+1555T>C		intron_variant	Intron 7 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32050 AN: 151970 Hom.: 3524 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.211 AC: 32065 AN: 152088 Hom.: 3528 Cov.: 33 AF XY: 0.217 AC XY: 16104 AN XY: 74354

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.200

Alfa AF: 0.206 Hom.: 1539

Bravo AF: 0.205

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.49

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: rs880028; hg19: chr7-50570136;