rs880028

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• aromatic L-amino acid decarboxylase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.206 AC: 8535 AN: 41488

American (AMR) AF: 0.212 AC: 3236 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3466

East Asian (EAS) AF: 0.113 AC: 585 AN: 5160

South Asian (SAS) AF: 0.189 AC: 909 AN: 4822

European-Finnish (FIN) AF: 0.318 AC: 3359 AN: 10566

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 14058 AN: 67980

Other (OTH) AF: 0.200 AC: 423 AN: 2114

Alfa AF: 0.207 Hom.: 1737

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
PhyloP100		-0.090
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs880028; hg19: chr7-50570136;