Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000033.4(ABCD1):c.900+2T>C

CA415100411

1172887 (ClinVar)

Gene: ABCD1 (HGNC:215)

Condition: adrenoleukodystrophy (MONDO:0018544)

Inheritance Mode: X-linked inheritance

UUID: 3eafa513-947d-4667-aa9d-21bc2fbf9158

Approved on: 2026-04-16

Published on: 2026-04-16

HGVS expressions

NM_000033.4:c.900+2T>C

NM_000033.4(ABCD1):c.900+2T>C

NC_000023.11:g.153726168T>C

CM000685.2:g.153726168T>C

NC_000023.10:g.152991623T>C

CM000685.1:g.152991623T>C

NC_000023.9:g.152644817T>C

NG_009022.2:g.6301T>C

NG_023231.1:g.3579A>G

ENST00000218104.6:c.900+2T>C

ENST00000218104.5:c.900+2T>C

ENST00000370129.4:c.345+2T>C

NM_000033.3:c.900+2T>C

Likely Pathogenic

PS1_Moderate PVS1_Strong PM2_Supporting

PM6 PM4 PM1 PM5 BS2 BS4 BS1 BS3 PS4 PS2 PS3 BP5 BP2 BP4 BA1 PP4 PP3 PP1

Evidence Links 0

Expert Panel

Peroxisomal Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Peroxisomal Disorders VCEP

The NM_000033.4:c.900+2T>C variant in ABCD1 occurs within the canonical splice donor site (+2) of intron 1. It is predicted to cause skipping of biologically-relevant-exon 1, resulting in an in-frame deletion (removes amino acids 1-300). However, it is predicted to escape nonsense mediated decay and remove >10% of the protein (PVS1_Strong). A different single nucleotide variant (c.900+2T>A) in the same canonical splice dinucleotide, expected to cause skipping of exon 1 (PMID 36180238), is classified as likely pathogenic for X-linked adrenoleukodystrophy by the ClinGen Peroxisomal Disorders VCEP (PS1_Moderate). This variant is absent from gnomADv4.1, gnomAD v3.1.2 and v.2.1.1 and therefore meets the criteria for PM2 Supporting (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for X-linked adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal VCEP: PVS1_Strong, PS1_Moderate, PM2_Supporting. (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)

PS1_Moderate

A different single nucleotide variant (c.900+2T>A) in the same canonical splice dinucleotide, expected to cause skipping of exon 1 (PMID 36180238), is classified as likely pathogenic for X-linked adrenoleukodystrophy by the ClinGen Peroxisomal Disorders VCEP (PS1_Moderate).

PVS1_Strong

The NM_000033.4:c.900+2T>G variant in ABCD1 occurs within the canonical splice donor site (+2) of intron 1. It is predicted to cause skipping of biologically-relevant-exon 1, resulting in an in-frame deletion (removes amino acids 1-300). However, it is predicted to escape nonsense mediated decay and remove >10% of the protein (PVS1_Strong).

PM2_Supporting

not in gnomAD

PM6

not confirmed (no studies)

PM4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM1

already counting PVS1

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS4

no studies

BS1

not in gnomAD

BS3

no studies

PS4

No frequencies reported

PS2

No clinical information, no confirmed de novo

PS3

No studies

BP5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP2

unknown/no studies

BP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BA1

not in gnomAD

PP4

only one known patient and no actual data on them/family

PP3

no computational evidence

PP1

only one known affected patient

Curation History

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