7-50550906-T-C

Variant names:

• chr7-50550906-T-C
• rs10499695
• NM_001082971.2:c.-28-6793A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001082971.2(DDC):​c.-28-6793A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,068 control chromosomes in the GnomAD database, including 17,709 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 0.48 (17709 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• aromatic L-amino acid decarboxylase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.-28-6793A>G		intron_variant	Intron 1 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.-28-6793A>G		intron_variant	Intron 1 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72728 AN: 151950 Hom.: 17674 Cov.: 33

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.479 AC: 72801 AN: 152068 Hom.: 17709 Cov.: 33 AF XY: 0.470 AC XY: 34936 AN XY: 74316

African (AFR) AF: 0.415 AC: 17199 AN: 41466

American (AMR) AF: 0.561 AC: 8571 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1976 AN: 3464

East Asian (EAS) AF: 0.480 AC: 2479 AN: 5168

South Asian (SAS) AF: 0.385 AC: 1857 AN: 4818

European-Finnish (FIN) AF: 0.382 AC: 4041 AN: 10568

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34871 AN: 67990

Other (OTH) AF: 0.511 AC: 1081 AN: 2116

Alfa AF: 0.501 Hom.: 10890

Bravo AF: 0.491

Asia WGS AF: 0.475 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.66
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10499695; hg19: chr7-50618604;