7-50504298-C-T

Position:

• chr7-50504298-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001082971.2(DDC):​c.715-239G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,978 control chromosomes in the GnomAD database, including 11,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (11526 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-50504298-C-T is Benign according to our data. Variant chr7-50504298-C-T is described in ClinVar as [Benign]. Clinvar id is 1271184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.715-239G>A		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.715-239G>A		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58669 AN: 151860 Hom.: 11515 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.386 AC: 58716 AN: 151978 Hom.: 11526 Cov.: 33 AF XY: 0.380 AC XY: 28248 AN XY: 74292

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.409

Alfa AF: 0.295 Hom.: 1063

Bravo AF: 0.386

Asia WGS AF: 0.396 AC: 1380 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.28

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: rs3823674; hg19: chr7-50571996;