7-50558201-C-T

Variant names:

• chr7-50558201-C-T
• rs7803788
• NM_001082971.2:c.-29+7084G>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+7084G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,640 control chromosomes in the GnomAD database, including 4,268 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 0.23 (4268 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.-29+7084G>A		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+7084G>A		intron_variant	Intron 1 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35101 AN: 151522 Hom.: 4267 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.281

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.231 AC: 35097 AN: 151640 Hom.: 4268 Cov.: 32 AF XY: 0.234 AC XY: 17342 AN XY: 74060

African (AFR) AF: 0.185 AC: 7651 AN: 41292

American (AMR) AF: 0.166 AC: 2529 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3472

East Asian (EAS) AF: 0.416 AC: 2134 AN: 5134

South Asian (SAS) AF: 0.319 AC: 1535 AN: 4816

European-Finnish (FIN) AF: 0.288 AC: 3015 AN: 10476

Middle Eastern (MID) AF: 0.274 AC: 79 AN: 288

European-Non Finnish (NFE) AF: 0.245 AC: 16654 AN: 67944

Other (OTH) AF: 0.222 AC: 468 AN: 2106

Alfa AF: 0.155 Hom.: 416

Bravo AF: 0.219

Asia WGS AF: 0.329 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.64
PhyloP100		-0.21
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: rs7803788; hg19: chr7-50625898;