NM_000033.4(ABCD1):c.848A>G (p.His283Arg) AND Adrenoleukodystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 26, 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:: RCV001958819.5

Allele description [Variation Report for NM_000033.4(ABCD1):c.848A>G (p.His283Arg)]

NM_000033.4(ABCD1):c.848A>G (p.His283Arg)

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.848A>G (p.His283Arg)

HGVS:

NC_000023.11:g.153726114A>G
NG_009022.2:g.6247A>G
NG_023231.1:g.3633T>C
NM_000033.4:c.848A>GMANE SELECT
NP_000024.2:p.His283Arg
LRG_1017t1:c.848A>G
LRG_1017:g.6247A>G
LRG_1017p1:p.His283Arg
NC_000023.10:g.152991569A>G

Protein change:

H283R

Links:

dbSNP: rs2148389929

NCBI 1000 Genomes Browser:

rs2148389929

Molecular consequence:

NM_000033.4:c.848A>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

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
SCV002244744	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 26, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16415970, 21300044, 20376793, 23469258, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002244744

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 26, 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

The genotype and phenotype studies of 40 Chinese patients with X-linked adrenoleukodystrophy (X-ALD).

Ping LL, Bao XH, Wang AH, Pan H, Wu Y, Xiong H, Zhang YH, Jiang YW, Qin J, Wu XR.

Beijing Da Xue Xue Bao Yi Xue Ban. 2006 Feb 18;38(1):66-70.

PubMed [citation]

PMID:: 16415970

Molecular diagnosis of X-linked adrenoleukodystrophy: experience from a clinical genetic laboratory in mainland China with report of 13 novel mutations.

Lan F, Wang Z, Xie H, Huang L, Ke L, Yang B, Zhu Z.

Clin Chim Acta. 2011 May 12;412(11-12):970-4. doi: 10.1016/j.cca.2011.01.036. Epub 2011 Feb 12.

PubMed [citation]

PMID:: 21300044

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002244744.3

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.His283 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16415970, 21300044). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1459053). This missense change has been observed in individual(s) with adrenoleukodystrophy (PMID: 20376793, 23469258). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 283 of the ABCD1 protein (p.His283Arg).

#	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 14, 2024

ClinVar

Relating variation to medicine