7-50463064-G-A

Position:

• chr7-50463064-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001082971.2(DDC):​c.*18+149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 693,788 control chromosomes in the GnomAD database, including 1,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (381 hom., cov: 32)
  • Exomes 𝑓: 0.072 (1613 hom.)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.676

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]

DDC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-50463064-G-A is Benign according to our data. Variant chr7-50463064-G-A is described in ClinVar as [Benign]. Clinvar id is 1256953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2	c.*18+149C>T		intron_variant		ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.*18+149C>T		intron_variant		1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9465 AN: 152112 Hom.: 383 Cov.: 32

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0719 AC: 38963 AN: 541558 Hom.: 1613 AF XY: 0.0713 AC XY: 20379 AN XY: 285682

Gnomad4 AFR exome AF: 0.0268

Gnomad4 AMR exome AF: 0.0748

Gnomad4 ASJ exome AF: 0.0894

Gnomad4 EAS exome AF: 0.0221

Gnomad4 SAS exome AF: 0.0470

Gnomad4 FIN exome AF: 0.0555

Gnomad4 NFE exome AF: 0.0826

Gnomad4 OTH exome AF: 0.0742

GnomAD4 genome AF: 0.0622 AC: 9464 AN: 152230 Hom.: 381 Cov.: 32 AF XY: 0.0602 AC XY: 4484 AN XY: 74440

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0725

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.0329

Gnomad4 SAS AF: 0.0410

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0831

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0763 Hom.: 441

Bravo AF: 0.0632

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 26, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.43

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: rs11575544; hg19: chr7-50530762;