NM_000033.4(ABCD1):c.1667A>G (p.Gln556Arg) AND Adrenoleukodystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 7, 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:: RCV003513722.2

Allele description [Variation Report for NM_000033.4(ABCD1):c.1667A>G (p.Gln556Arg)]

NM_000033.4(ABCD1):c.1667A>G (p.Gln556Arg)

Gene:

ABCD1:ATP binding cassette subfamily D member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000033.4(ABCD1):c.1667A>G (p.Gln556Arg)

HGVS:

NC_000023.11:g.153740606A>G
NG_009022.2:g.20739A>G
NG_147800.1:g.226A>G
NM_000033.4:c.1667A>GMANE SELECT
NP_000024.2:p.Gln556Arg
LRG_1017t1:c.1667A>G
LRG_1017:g.20739A>G
LRG_1017p1:p.Gln556Arg
NC_000023.10:g.153006060A>G

Protein change:

Q556R

Molecular consequence:

NM_000033.4:c.1667A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Adrenoleukodystrophy (ALD)
Synonyms:: ADDISON DISEASE AND CEREBRAL SCLEROSIS; BRONZE SCHILDER DISEASE; MELANODERMIC LEUKODYSTROPHY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018544; MedGen: C0162309; OMIM: 300100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004298785	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10980539, 14767898, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004298785

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 7, 2023)

germline

clinical testing

PubMed (3)
[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

Detection of mutations in the ALD gene (ABCD1) in seven Italian families: description of four novel mutations.

Lira MG, Mottes M, Pignatti PF, Medica I, Uziel G, Cappa M, Bertini E, Rizzuto N, Salviati A.

Hum Mutat. 2000 Sep;16(3):271.

PubMed [citation]

PMID:: 10980539

[X-linked adrenoleukodystrophy ABCD1 gene mutation analysis in China].

Pan H, Xiong H, Zhang YH, Wu Y, Bao XH, Jiang YW, Wu XR.

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004 Feb;21(1):1-4. Chinese.

PubMed [citation]

PMID:: 14767898

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298785.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 556 of the ABCD1 protein (p.Gln556Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with adrenoleukodystrophy (PMID: 10980539, 14767898). 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) performed at Invitae indicates that this missense variant is expected to disrupt ABCD1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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