rs6593011

Variant names:

• chr7-50565099-C-A
• rs6593011
• NM_001082971.2:c.-29+186G>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.-29+186G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,090 control chromosomes in the GnomAD database, including 4,182 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 (4182 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.-29+186G>T		intron_variant	Intron 1 of 14	ENST00000444124.7	NP_001076440.2
DDC	XM_047419932.1	c.-29+186G>T		intron_variant	Intron 1 of 15		XP_047275888.1
DDC	XM_047419931.1	c.-29+186G>T		intron_variant	Intron 1 of 13		XP_047275887.1
DDC	XM_005271745.5	c.-29+186G>T		intron_variant	Intron 1 of 13		XP_005271802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.-29+186G>T		intron_variant	Intron 1 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31437 AN: 151972 Hom.: 4171 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0368

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.207 AC: 31458 AN: 152090 Hom.: 4182 Cov.: 33 AF XY: 0.201 AC XY: 14957 AN XY: 74340

African (AFR) AF: 0.379 AC: 15717 AN: 41438

American (AMR) AF: 0.187 AC: 2863 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3468

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5184

South Asian (SAS) AF: 0.156 AC: 753 AN: 4824

European-Finnish (FIN) AF: 0.0849 AC: 899 AN: 10590

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10063 AN: 67990

Other (OTH) AF: 0.203 AC: 427 AN: 2106

Alfa AF: 0.166 Hom.: 10361

Bravo AF: 0.221

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.90
DANN	Benign	0.45
PhyloP100		-0.077
PromoterAI		0.019	Neutral
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: rs6593011; hg19: chr7-50632796;