rs6592961

Positions:

• chr7-50505192-G-A
• chr7-50505192-G-T

Variant summary

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

The NM_001082971.2(DDC):​c.715-1133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,036 control chromosomes in the GnomAD database, including 6,295 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 0.28 (6295 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.715-1133C>T		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.715-1133C>T		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41934 AN: 151918 Hom.: 6269 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.276 AC: 42013 AN: 152036 Hom.: 6295 Cov.: 33 AF XY: 0.284 AC XY: 21121 AN XY: 74290

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.248

Alfa AF: 0.220 Hom.: 7931

Bravo AF: 0.281

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.056
DANN	Benign	0.42

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: rs6592961; hg19: chr7-50572890;