rs12718541

Variant names:

• chr7-50482446-A-G
• rs12718541
• NM_001082971.2:c.945-2583T>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.945-2583T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,990 control chromosomes in the GnomAD database, including 23,289 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 0.55 (23289 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 18 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.945-2583T>C		intron_variant	Intron 9 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.945-2583T>C		intron_variant	Intron 9 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83702 AN: 151872 Hom.: 23247 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.551 AC: 83806 AN: 151990 Hom.: 23289 Cov.: 32 AF XY: 0.546 AC XY: 40601 AN XY: 74302

African (AFR) AF: 0.523 AC: 21641 AN: 41400

American (AMR) AF: 0.620 AC: 9467 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2127 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2297 AN: 5176

South Asian (SAS) AF: 0.513 AC: 2476 AN: 4822

European-Finnish (FIN) AF: 0.479 AC: 5053 AN: 10552

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38987 AN: 67986

Other (OTH) AF: 0.571 AC: 1203 AN: 2106

Alfa AF: 0.569 Hom.: 96608

Bravo AF: 0.558

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.0
DANN	Benign	0.50
PhyloP100		0.58
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: rs12718541; hg19: chr7-50550144;