NM_001082971.2(DDC):c.286G>A (p.Gly96Arg) AND Deficiency of aromatic-L-amino-acid decarboxylase

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Apr 11, 2023
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:: RCV001250057.3

Allele description [Variation Report for NM_001082971.2(DDC):c.286G>A (p.Gly96Arg)]

NM_001082971.2(DDC):c.286G>A (p.Gly96Arg)

Genes:

DDC-AS1:DDC antisense RNA 1 [Gene - HGNC]
DDC:dopa decarboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p12.1

Genomic location:

Preferred name:

NM_001082971.2(DDC):c.286G>A (p.Gly96Arg)

HGVS:

NC_000007.14:g.50539944C>T
NG_008742.1:g.30513G>A
NM_000790.4:c.286G>A
NM_001082971.2:c.286G>AMANE SELECT
NM_001242886.2:c.202-1965G>A
NM_001242887.2:c.286G>A
NM_001242888.2:c.201+3941G>A
NM_001242889.2:c.286G>A
NM_001242890.2:c.286G>A
NP_000781.2:p.Gly96Arg
NP_001076440.2:p.Gly96Arg
NP_001229816.2:p.Gly96Arg
NP_001229818.2:p.Gly96Arg
NP_001229819.2:p.Gly96Arg
NC_000007.13:g.50607642C>T
NC_000007.13:g.50607642C>T
NM_000790.3:c.286G>A
NR_033845.1:n.292C>T

Protein change:

G96R

Links:

dbSNP: rs1285477390

NCBI 1000 Genomes Browser:

rs1285477390

Molecular consequence:

NM_001242886.2:c.202-1965G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001242888.2:c.201+3941G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000790.4:c.286G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001082971.2:c.286G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001242887.2:c.286G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001242889.2:c.286G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001242890.2:c.286G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_033845.1:n.292C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001424209	Elsea Laboratory, Baylor College of Medicine	no assertion criteria provided	Likely pathogenic (Apr 1, 2020)	maternal	clinical testing
SCV003497592	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25956449, 28856607, 32369189, 31953134, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001424209

Elsea Laboratory, Baylor College of Medicine

no assertion criteria provided

Likely pathogenic
(Apr 1, 2020)

maternal

clinical testing

SCV003497592

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Apr 11, 2023)

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
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Aromatic L-amino acid decarboxylase deficiency diagnosed by clinical metabolomic profiling of plasma.

Atwal PS, Donti TR, Cardon AL, Bacino CA, Sun Q, Emrick L, Reid Sutton V, Elsea SH.

Mol Genet Metab. 2015 Jun-Jul;115(2-3):91-4. doi: 10.1016/j.ymgme.2015.04.008. Epub 2015 May 2.

PubMed [citation]

PMID:: 25956449

Natural History of Aromatic L-Amino Acid Decarboxylase Deficiency in Taiwan.

Hwu WL, Chien YH, Lee NC, Li MH.

JIMD Rep. 2018;40:1-6. doi: 10.1007/8904_2017_54. Epub 2017 Aug 31.

PubMed [citation]

PMID:: 28856607
PMCID:: PMC6122029

See all PubMed Citations (5)

Details of each submission

From Elsea Laboratory, Baylor College of Medicine, SCV001424209.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Invitae, SCV003497592.2

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

Description

This missense change has been observed in individual(s) with aromatic L-amino acid decarboxylase deficiency (PMID: 25956449, 28856607, 32369189). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects DDC function (PMID: 31953134). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DDC protein function. ClinVar contains an entry for this variant (Variation ID: 973440). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 96 of the DDC protein (p.Gly96Arg).

#	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: Feb 20, 2024

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