rs3757472

chr7-50470285-A-Cchr7-50470285-A-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.1042-114T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 785,856 control chromosomes in the GnomAD database, including 179,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33811 hom., cov: 33)
  • Exomes 𝑓: 0.68 (145864 hom.)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.494

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=-0.89).
• BP6: Variant 7-50470285-A-C is Benign according to our data. Variant chr7-50470285-A-C is described in ClinVar as [Benign]. Clinvar id is 1245994.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.1042-114T>G		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.1042-114T>G		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100918 AN: 152100 Hom.: 33767 Cov.: 33

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.659

GnomAD4 exome AF: 0.676 AC: 428028 AN: 633638 Hom.: 145864 AF XY: 0.671 AC XY: 230332 AN XY: 343042

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.689

Gnomad4 EAS exome AF: 0.520

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.664 AC: 101026 AN: 152218 Hom.: 33811 Cov.: 33 AF XY: 0.668 AC XY: 49680 AN XY: 74424

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.657

Alfa AF: 0.650 Hom.: 6316

Bravo AF: 0.659

Asia WGS AF: 0.615 AC: 2138 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	-0.89
Cadd	Benign	1.5
Dann	Benign	0.29

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: rs3757472; hg19: chr7-50537983; COSMIC: COSV63567991;