NM_000033.4(ABCD1):c.1792_1793del (p.Met598fs) AND Adrenoleukodystrophy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 24, 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:: RCV000012061.5

Allele description [Variation Report for NM_000033.4(ABCD1):c.1792_1793del (p.Met598fs)]

NM_000033.4(ABCD1):c.1792_1793del (p.Met598fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000033.4(ABCD1):c.1792_1793del (p.Met598fs)

HGVS:

NC_000023.11:g.153742998_153742999del
NG_009022.2:g.23131_23132del
NM_000033.4:c.1792_1793delMANE SELECT
NP_000024.2:p.Met598fs
LRG_1017t1:c.1792_1793del
LRG_1017:g.23131_23132del
LRG_1017p1:p.Met598fs
NC_000023.10:g.153008451_153008452del
NC_000023.10:g.153008452_153008453del

Protein change:

M598fs

Links:

OMIM: 300371.0018; dbSNP: rs2148398995

NCBI 1000 Genomes Browser:

rs2148398995

Molecular consequence:

NM_000033.4:c.1792_1793del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000032295	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 1994)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004298788	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 24, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11748843, 8040304, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000032295

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 1994)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV004298788

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 24, 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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations.

Kemp S, Pujol A, Waterham HR, van Geel BM, Boehm CD, Raymond GV, Cutting GR, Wanders RJ, Moser HW.

Hum Mutat. 2001 Dec;18(6):499-515. Review.

PubMed [citation]

PMID:: 11748843

Identification of mutations in the putative ATP-binding domain of the adrenoleukodystrophy gene.

Fanen P, Guidoux S, Sarde CO, Mandel JL, Goossens M, Aubourg P.

J Clin Invest. 1994 Aug;94(2):516-20.

PubMed [citation]

PMID:: 8040304
PMCID:: PMC296124

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000032295.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a family in which 2 brothers had cerebral adrenoleukodystrophy (ALD; 300100), one at age 7 years and the other at age 9 years, Fanen et al. (1994) identified a 2-bp (TA) deletion at nucleotide 2177 of the ALD gene, leading to a termination codon at position 599 in exon 8 and a truncated protein.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298788.1

#	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 creates a premature translational stop signal (p.Met598Valfs*2) in the ABCD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCD1 are known to be pathogenic (PMID: 11748843). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with cerebral adrenomyeloneuropathy (PMID: 8040304). This variant is also known as 2177delTA. ClinVar contains an entry for this variant (Variation ID: 11309). 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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