rs3829897

Variant names:

• chr7-50562067-G-T
• rs3829897
• NM_001082971.2:c.-29+3218C>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+3218C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,016 control chromosomes in the GnomAD database, including 17,329 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 0.47 (17329 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 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+3218C>A		intron	N/A	NP_001076440.2	A0A0S2Z3N4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.-29+3218C>A		intron	N/A	ENSP00000403644.2	P20711-1
	DDC	ENST00000897740.1		c.-29+3218C>A		intron	N/A	ENSP00000567799.1
	DDC	ENST00000897739.1		c.-29+3218C>A		intron	N/A	ENSP00000567798.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70963 AN: 151898 Hom.: 17301 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.467 AC: 71042 AN: 152016 Hom.: 17329 Cov.: 33 AF XY: 0.477 AC XY: 35408 AN XY: 74306

African (AFR) AF: 0.586 AC: 24279 AN: 41436

American (AMR) AF: 0.423 AC: 6463 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3470

East Asian (EAS) AF: 0.622 AC: 3215 AN: 5168

South Asian (SAS) AF: 0.505 AC: 2431 AN: 4812

European-Finnish (FIN) AF: 0.547 AC: 5777 AN: 10568

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26446 AN: 67970

Other (OTH) AF: 0.422 AC: 891 AN: 2112

Alfa AF: 0.412 Hom.: 8200

Bravo AF: 0.465

Asia WGS AF: 0.515 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.39
PhyloP100		-1.2
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: rs3829897; hg19: chr7-50629764; COSMIC: COSV63566029; COSMIC: COSV63566029;