rs2044859

Positions:

• chr7-50544864-G-A
• chr7-50544864-G-C

Variant summary

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

The NM_001082971.2(DDC):​c.-28-751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,066 control chromosomes in the GnomAD database, including 29,498 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 0.62 (29498 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2	c.-28-751C>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.-28-751C>T		intron_variant		1	NM_001082971.2	ENSP00000403644	P1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94081 AN: 151948 Hom.: 29471 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.619 AC: 94151 AN: 152066 Hom.: 29498 Cov.: 32 AF XY: 0.624 AC XY: 46361 AN XY: 74348

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.635

Alfa AF: 0.633 Hom.: 5144

Bravo AF: 0.618

Asia WGS AF: 0.606 AC: 2110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.40

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: rs2044859; hg19: chr7-50612562;