rs6263

Positions:

chr7-50528202-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001082971.2(DDC):c.649A>G(p.Met217Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,614,074 control chromosomes in the GnomAD database, including 590 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 Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 100 hom., cov: 32)

Exomes 𝑓: 0.022 ( 490 hom. )

Consequence

DDC
NM_001082971.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.03

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021415353).

BP6

Variant 7-50528202-T-C is Benign according to our data. Variant chr7-50528202-T-C is described in ClinVar as [Benign]. Clinvar id is 360434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-50528202-T-C is described in Lovd as [Benign]. Variant chr7-50528202-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2 linkuse as main transcript	c.649A>G	p.Met217Val	missense_variant	6/15	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7 linkuse as main transcript	c.649A>G	p.Met217Val	missense_variant	6/15	1	NM_001082971.2	ENSP00000403644	P1	P20711-1

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4535

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0417

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.0786

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0205

GnomAD3 exomes

AF:

0.0270

AC:

6792

AN:

251456

Hom.:

165

AF XY:

0.0261

AC XY:

3551

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0407

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.0688

Gnomad SAS exome

AF:

0.0127

Gnomad FIN exome

AF:

0.0646

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0217

AC:

31756

AN:

1461764

Hom.:

490

Cov.:

AF XY:

0.0213

AC XY:

15486

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0404

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.0285

Gnomad4 EAS exome

AF:

0.0732

Gnomad4 SAS exome

AF:

0.0129

Gnomad4 FIN exome

AF:

0.0622

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0229

GnomAD4 genome

AF:

0.0298

AC:

4545

AN:

152310

Hom.:

100

Cov.:

AF XY:

0.0315

AC XY:

2344

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0418

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.0788

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0673

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0273

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0187

AC:

ESP6500AA

AF:

0.0386

AC:

170

ESP6500EA

AF:

0.0153

AC:

132

ExAC

AF:

0.0265

AC:

3213

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

EpiCase

AF:

0.0174

EpiControl

AF:

0.0138

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Deficiency of aromatic-L-amino-acid decarboxylase

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.20

T;.;.;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.037

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.85

.;T;T;T;T

MetaRNN

Benign

0.0021

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.17

N;.;.;N;N

MutationTaster

Benign

0.96

D;D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.0

N;.;N;N;N

REVEL

Benign

0.098

Sift

Benign

0.066

T;.;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T

Polyphen

0.0020

B;.;.;B;.

Vest4

0.064

MPC

0.29

ClinPred

0.013

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.35

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over