NM_001082971.2(DDC):c.1123C>T (p.Gln375Ter) AND Deficiency of aromatic-L-amino-acid decarboxylase

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 20, 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:: RCV003838905.1

Allele description [Variation Report for NM_001082971.2(DDC):c.1123C>T (p.Gln375Ter)]

NM_001082971.2(DDC):c.1123C>T (p.Gln375Ter)

Gene:

DDC:dopa decarboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p12.2

Genomic location:

Preferred name:

NM_001082971.2(DDC):c.1123C>T (p.Gln375Ter)

HGVS:

NC_000007.14:g.50470090G>A
NG_008742.1:g.100367C>T
NM_000790.4:c.1123C>T
NM_001082971.2:c.1123C>TMANE SELECT
NM_001242886.2:c.1009C>T
NM_001242887.2:c.979C>T
NM_001242888.2:c.889C>T
NM_001242889.2:c.844C>T
NP_000781.2:p.Gln375Ter
NP_001076440.2:p.Gln375Ter
NP_001229815.2:p.Gln337Ter
NP_001229816.2:p.Gln327Ter
NP_001229817.2:p.Gln297Ter
NP_001229818.2:p.Gln282Ter
NC_000007.13:g.50537788G>A

Protein change:

Q282*

Links:

dbSNP: rs777681757

NCBI 1000 Genomes Browser:

rs777681757

Molecular consequence:

NM_000790.4:c.1123C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001082971.2:c.1123C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001242886.2:c.1009C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001242887.2:c.979C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001242888.2:c.889C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001242889.2:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004636671	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 20, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30952622, 15079002, 24788355, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004636671

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 20, 2023)

germline

clinical testing

PubMed (4)
[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 amino acid decarboxylase deficiency: Molecular and metabolic basis and therapeutic outlook.

Himmelreich N, Montioli R, Bertoldi M, Carducci C, Leuzzi V, Gemperle C, Berner T, Hyland K, Thöny B, Hoffmann GF, Voltattorni CB, Blau N.

Mol Genet Metab. 2019 May;127(1):12-22. doi: 10.1016/j.ymgme.2019.03.009. Epub 2019 Mar 27. Review. Erratum in: Mol Genet Metab. 2021 Sep-Oct;134(1-2):216. doi: 10.1016/j.ymgme.2021.06.010.

PubMed [citation]

PMID:: 30952622

Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis.

Pons R, Ford B, Chiriboga CA, Clayton PT, Hinton V, Hyland K, Sharma R, De Vivo DC.

Neurology. 2004 Apr 13;62(7):1058-65. Review.

PubMed [citation]

PMID:: 15079002

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004636671.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is present in population databases (rs777681757, gnomAD 0.02%). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1324214). This premature translational stop signal has been observed in individual(s) with aromatic L-amino acid decarboxylase deficiency (PMID: 30952622). This sequence change creates a premature translational stop signal (p.Gln375*) in the DDC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DDC are known to be pathogenic (PMID: 15079002, 24788355).

#	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: Mar 5, 2024

ClinVar

Relating variation to medicine