7-50463289-C-T

Variant names:

• chr7-50463289-C-T
• rs11575542
• NM_001082971.2:c.1385G>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.1385G>A​(p.Arg462Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,614,172 control chromosomes in the GnomAD database, including 1,143 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (478 hom., cov: 32)
  • Exomes 𝑓: 0.019 (665 hom.)
• Consequence: DDC NM_001082971.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.227

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012446344).
• BP6: Variant 7-50463289-C-T is Benign according to our data. Variant chr7-50463289-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 360429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-50463289-C-T is described in Lovd as [Benign]. Variant chr7-50463289-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.1385G>A	p.Arg462Gln	missense_variant	Exon 14 of 15	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.1385G>A	p.Arg462Gln	missense_variant	Exon 14 of 15	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7944 AN: 152208 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00857

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0378

GnomAD3 exomes AF: 0.0227 AC: 5712 AN: 251162 Hom.: 208 AF XY: 0.0208 AC XY: 2822 AN XY: 135810

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.00903

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0132

Gnomad FIN exome AF: 0.00869

Gnomad NFE exome AF: 0.0180

Gnomad OTH exome AF: 0.0178

GnomAD4 exome AF: 0.0190 AC: 27816 AN: 1461846 Hom.: 665 Cov.: 32 AF XY: 0.0185 AC XY: 13428 AN XY: 727220

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.00846

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0143

Gnomad4 FIN exome AF: 0.00942

Gnomad4 NFE exome AF: 0.0166

Gnomad4 OTH exome AF: 0.0243

GnomAD4 genome AF: 0.0524 AC: 7978 AN: 152326 Hom.: 478 Cov.: 32 AF XY: 0.0504 AC XY: 3755 AN XY: 74490

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0283

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.00857

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0204 Hom.: 192

Bravo AF: 0.0574

TwinsUK AF: 0.0121 AC: 45

ALSPAC AF: 0.0163 AC: 63

ESP6500AA AF: 0.151 AC: 664

ESP6500EA AF: 0.0149 AC: 128

ExAC AF: 0.0263 AC: 3192

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31177555, 30911067) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:2

Dec 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Deficiency of aromatic-L-amino-acid decarboxylase Benign:2

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

DDC-related disorder Benign:1

Nov 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.022
DANN	Benign	0.91
DEOGEN2	Benign	0.10	T;.;T;.;.;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.027	N
LIST_S2	Uncertain	0.86	.;D;D;D;.;D;D
MetaRNN	Benign	0.0012	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;.;.;.;.;.;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.23	N;.;.;.;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.14	T;.;.;.;T;T;T
Sift4G	Benign	0.35	T;T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;.;.;B
Vest4		0.012
MPC		0.33
ClinPred		0.00045	T
GERP RS		-4.2
Varity_R		0.053
gMVP		0.44

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: rs11575542; hg19: chr7-50530987;