rs9942686

Variant names:

• chr7-50528683-G-A
• rs9942686
• NM_001082971.2:c.571-403C>T

Variant summary

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

The NM_001082971.2(DDC):​c.571-403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,954 control chromosomes in the GnomAD database, including 3,793 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 0.22 (3793 hom., cov: 31)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.571-403C>T		intron_variant	Intron 5 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.571-403C>T		intron_variant	Intron 5 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33300 AN: 151836 Hom.: 3793 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.219 AC: 33294 AN: 151954 Hom.: 3793 Cov.: 31 AF XY: 0.219 AC XY: 16256 AN XY: 74248

African (AFR) AF: 0.215 AC: 8897 AN: 41444

American (AMR) AF: 0.162 AC: 2480 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3464

East Asian (EAS) AF: 0.394 AC: 2030 AN: 5152

South Asian (SAS) AF: 0.308 AC: 1482 AN: 4808

European-Finnish (FIN) AF: 0.200 AC: 2113 AN: 10552

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14825 AN: 67942

Other (OTH) AF: 0.216 AC: 456 AN: 2114

Alfa AF: 0.224 Hom.: 500

Bravo AF: 0.216

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.37
DANN	Benign	0.20
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9942686; hg19: chr7-50596381;