7-50531005-T-C

Position:

• chr7-50531005-T-C

Variant summary

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

The NM_001082971.2(DDC):​c.436-1663A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,098 control chromosomes in the GnomAD database, including 34,411 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 0.66 (34411 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2	c.436-1663A>G		intron_variant		ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.436-1663A>G		intron_variant		1	NM_001082971.2	ENSP00000403644	P1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101051 AN: 151980 Hom.: 34409 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.665 AC: 101080 AN: 152098 Hom.: 34411 Cov.: 32 AF XY: 0.655 AC XY: 48722 AN XY: 74354

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.809

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.694

Alfa AF: 0.726 Hom.: 38325

Bravo AF: 0.658

Asia WGS AF: 0.753 AC: 2619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.46

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: rs10244632; hg19: chr7-50598703;