NM_001082971.2(DDC):c.68G>T (p.Gly23Val) AND Deficiency of aromatic-L-amino-acid decarboxylase

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 2, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002471920.2

Allele description [Variation Report for NM_001082971.2(DDC):c.68G>T (p.Gly23Val)]

NM_001082971.2(DDC):c.68G>T (p.Gly23Val)

Gene:

DDC:dopa decarboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p12.1

Genomic location:

Preferred name:

NM_001082971.2(DDC):c.68G>T (p.Gly23Val)

HGVS:

NC_000007.14:g.50544018C>A
NG_008742.2:g.26387G>T
NM_000790.4:c.68G>T
NM_001082971.2:c.68G>TMANE SELECT
NM_001242886.2:c.68G>T
NM_001242887.2:c.68G>T
NM_001242888.2:c.68G>T
NM_001242889.2:c.68G>T
NM_001242890.2:c.68G>T
NP_000781.2:p.Gly23Val
NP_001076440.2:p.Gly23Val
NP_001229815.2:p.Gly23Val
NP_001229816.2:p.Gly23Val
NP_001229817.2:p.Gly23Val
NP_001229818.2:p.Gly23Val
NP_001229819.2:p.Gly23Val
NC_000007.13:g.50611716C>A
NG_008742.1:g.26439G>T
NM_001082971.1:c.68G>T

Protein change:

G23V

Molecular consequence:

NM_000790.4:c.68G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001082971.2:c.68G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242886.2:c.68G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242887.2:c.68G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242888.2:c.68G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242889.2:c.68G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242890.2:c.68G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Deficiency of aromatic-L-amino-acid decarboxylase
Synonyms:: DDC deficiency; Aromatic amino acid decarboxylase deficiency; Dopa decarboxylase deficiency
Identifiers:: MONDO: MONDO:0012084; MedGen: C1291564; Orphanet: 35708; OMIM: 608643

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002767562	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 2, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17240182, 24865461, 31104889, 33808712, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002767562

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 2, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes.

Verbeek MM, Geurtz PB, Willemsen MA, Wevers RA.

Mol Genet Metab. 2007 Apr;90(4):363-9. Epub 2007 Jan 19.

PubMed [citation]

PMID:: 17240182

A comprehensive picture of the mutations associated with aromatic amino acid decarboxylase deficiency: from molecular mechanisms to therapy implications.

Montioli R, Dindo M, Giorgetti A, Piccoli S, Cellini B, Voltattorni CB.

Hum Mol Genet. 2014 Oct 15;23(20):5429-40. doi: 10.1093/hmg/ddu266. Epub 2014 May 27.

PubMed [citation]

PMID:: 24865461

See all PubMed Citations (5)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767562.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with aromatic L-amino acid decarboxylase deficiency (AADC deficiency) (MIM#608643) (PMID: 33808712, PMID: 31104889, PMID: 24865461, PMID: 17240182). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to valine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1005 - Clinically accredited laboratory assay specific to gene product shows abnormal protein function. This individual's CSF neurotransmitter tests are in keeping with AADC deficiency (The Children’s Hospital at Westmead). (SP) 1102 - Strong phenotype match for this individual. (SP) 1201 - Heterozygous variant detected in trans with a second pathogenic heterozygous variant (c.1339C>T; p.Arg447Cys) in a recessive disease. (SP) 1205 - This variant has been shown to be maternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

ClinVar

Relating variation to medicine