rs921451

Variant names:

• chr7-50555587-T-C
• rs921451
• NM_001082971.2:c.-29+9698A>G

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+9698A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,816 control chromosomes in the GnomAD database, including 8,410 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 0.32 (8410 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 45 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.-29+9698A>G		intron_variant	Intron 1 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.-29+9698A>G		intron_variant	Intron 1 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48611 AN: 151698 Hom.: 8400 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.320 AC: 48627 AN: 151816 Hom.: 8410 Cov.: 32 AF XY: 0.332 AC XY: 24596 AN XY: 74164

African (AFR) AF: 0.220 AC: 9101 AN: 41446

American (AMR) AF: 0.253 AC: 3867 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3466

East Asian (EAS) AF: 0.482 AC: 2475 AN: 5134

South Asian (SAS) AF: 0.461 AC: 2219 AN: 4812

European-Finnish (FIN) AF: 0.530 AC: 5560 AN: 10488

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23402 AN: 67896

Other (OTH) AF: 0.298 AC: 630 AN: 2112

Alfa AF: 0.330 Hom.: 13218

Bravo AF: 0.296

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.33
PhyloP100		-0.28
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: rs921451; hg19: chr7-50623285;