7-50562573-C-T

Variant names:

• chr7-50562573-C-T
• rs10278338
• NM_001082971.2:c.-29+2712G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001082971.2(DDC):​c.-29+2712G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,100 control chromosomes in the GnomAD database, including 10,829 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 (10829 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.902
• Publications: 9 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 (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	NM_001082971.2	MANE Select	c.-29+2712G>A		intron	N/A	NP_001076440.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.-29+2712G>A		intron	N/A	ENSP00000403644.2
	DDC	ENST00000897740.1		c.-29+2712G>A		intron	N/A	ENSP00000567799.1
	DDC	ENST00000897739.1		c.-29+2712G>A		intron	N/A	ENSP00000567798.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56098 AN: 151982 Hom.: 10808 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.369 AC: 56148 AN: 152100 Hom.: 10829 Cov.: 33 AF XY: 0.380 AC XY: 28262 AN XY: 74330

African (AFR) AF: 0.319 AC: 13242 AN: 41502

American (AMR) AF: 0.329 AC: 5025 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1038 AN: 3464

East Asian (EAS) AF: 0.581 AC: 2992 AN: 5146

South Asian (SAS) AF: 0.476 AC: 2297 AN: 4828

European-Finnish (FIN) AF: 0.540 AC: 5715 AN: 10588

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24742 AN: 67962

Other (OTH) AF: 0.339 AC: 717 AN: 2116

Alfa AF: 0.356 Hom.: 1732

Bravo AF: 0.353

Asia WGS AF: 0.469 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.31
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10278338; hg19: chr7-50630270;