chr7-50477395-T-C

Position:

• chr7-50477395-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.1022-752A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,012 control chromosomes in the GnomAD database, including 23,631 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 0.56 (23631 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.1022-752A>G		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.1022-752A>G		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84327 AN: 151894 Hom.: 23589 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.555 AC: 84432 AN: 152012 Hom.: 23631 Cov.: 32 AF XY: 0.553 AC XY: 41054 AN XY: 74282

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.575

Alfa AF: 0.559 Hom.: 4474

Bravo AF: 0.558

Asia WGS AF: 0.531 AC: 1848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.41

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: rs3887825; hg19: chr7-50545093;