This VCEP application contains twenty genes in which defects cause peroxisome biogenesis disorders and related single enzyme/protein defects. Variant curation will proceed in a tiered approach, starting with (1) the most common genes in which defects occur, (2) genes that have variants with unusual phenotypes, and (3) genes in which disease causing variants have moderate evidence (but more evidence may become available by the time of curation). Note that all tiers include conditions expected to be picked on newborn screening by elevated very long chain fatty acids.

Tier 1. ABCD1, PEX1, PEX6, PEX26, PEX7, HSD17B4

Tier 2. PEX2, PEX10, PEX12, PEX16

Tier 3. PEX3, PEX5, PEX11B, PEX13, PEX14, PEX19, ACOX1, PHYH, AGPS, GNPAT

Step 2 Approval:

• September 1, 2023 - VCEP received approval to pilot ACMG/AMP specifications for ABCD1.