rs3779084

Variant names:

• chr7-50501037-A-G
• rs3779084
• NM_001082971.2:c.782-1795T>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.782-1795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,116 control chromosomes in the GnomAD database, including 3,653 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 (3653 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 17 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 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.782-1795T>C		intron	N/A	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.782-1795T>C		intron	N/A	NP_000781.2	P20711-1
	DDC	NM_001242886.2		c.668-1795T>C		intron	N/A	NP_001229815.2	A0A087WV24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.782-1795T>C		intron	N/A	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.782-1795T>C		intron	N/A	ENSP00000350616.5	P20711-1
	DDC	ENST00000380984.4	TSL:1	c.782-1795T>C		intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32615 AN: 151998 Hom.: 3649 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.214 AC: 32624 AN: 152116 Hom.: 3653 Cov.: 32 AF XY: 0.220 AC XY: 16383 AN XY: 74354

African (AFR) AF: 0.219 AC: 9094 AN: 41484

American (AMR) AF: 0.213 AC: 3257 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3470

East Asian (EAS) AF: 0.112 AC: 577 AN: 5164

South Asian (SAS) AF: 0.188 AC: 905 AN: 4818

European-Finnish (FIN) AF: 0.317 AC: 3359 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14054 AN: 67976

Other (OTH) AF: 0.196 AC: 415 AN: 2112

Alfa AF: 0.207 Hom.: 1746

Bravo AF: 0.209

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.41
DANN	Benign	0.49
PhyloP100		-0.44
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3779084;

hg19: chr7-50568735;