NM_000033.4(ABCD1):c.1961T>C (p.Leu654Pro) AND Adrenoleukodystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 31, 2019
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:: RCV001041737.2

Allele description [Variation Report for NM_000033.4(ABCD1):c.1961T>C (p.Leu654Pro)]

NM_000033.4(ABCD1):c.1961T>C (p.Leu654Pro)

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.1961T>C (p.Leu654Pro)

HGVS:

NC_000023.11:g.153743316T>C
NG_009022.2:g.23449T>C
NM_000033.4:c.1961T>CMANE SELECT
NP_000024.2:p.Leu654Pro
LRG_1017t1:c.1961T>C
LRG_1017:g.23449T>C
LRG_1017p1:p.Leu654Pro
NC_000023.10:g.153008770T>C
NM_000033.3:c.1961T>C

Protein change:

L654P

Links:

dbSNP: rs2091774046

NCBI 1000 Genomes Browser:

rs2091774046

Molecular consequence:

NM_000033.4:c.1961T>C - 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
SCV001205370	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 31, 2019)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 24480483, 15800013, 27067449, 11748843, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001205370

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 31, 2019)

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

X-linked adrenoleukodystrophy in women: a cross-sectional cohort study.

Engelen M, Barbier M, Dijkstra IM, Schür R, de Bie RM, Verhamme C, Dijkgraaf MG, Aubourg PA, Wanders RJ, van Geel BM, de Visser M, Poll-The BT, Kemp S.

Brain. 2014 Mar;137(Pt 3):693-706. doi: 10.1093/brain/awt361. Epub 2014 Jan 29.

PubMed [citation]

PMID:: 24480483

Decreased expression of ABCD4 and BG1 genes early in the pathogenesis of X-linked adrenoleukodystrophy.

Asheuer M, Bieche I, Laurendeau I, Moser A, Hainque B, Vidaud M, Aubourg P.

Hum Mol Genet. 2005 May 15;14(10):1293-303. Epub 2005 Mar 30.

PubMed [citation]

PMID:: 15800013

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001205370.1

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

Description

This sequence change replaces leucine with proline at codon 654 of the ABCD1 protein (p.Leu654Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with adrenoleukodystrophy (PMID: 11748843 15800013, 24480483, 27067449). This variant has been reported to affect ABCD1 protein function (PMID: 27067449). 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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