rs6951648

chr7-50499795-G-Achr7-50499795-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001082971.2(DDC):c.782-553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,110 control chromosomes in the GnomAD database, including 2,885 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 0.19 (2885 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.782-553C>T		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.782-553C>T		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29211 AN: 151992 Hom.: 2890 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.192 AC: 29208 AN: 152110 Hom.: 2885 Cov.: 32 AF XY: 0.190 AC XY: 14107 AN XY: 74372

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0441

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.190

Alfa AF: 0.199 Hom.: 2947

Bravo AF: 0.194

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.0
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs6951648; hg19: chr7-50567493;