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_000350.3:c.885del

CA958684

438109 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: 65bb8769-0196-4a65-9d3c-fe9ef1f9123e

Approved on: 2026-07-28

Published on: 2026-07-28

HGVS expressions

NM_000350.3:c.885del

NC_000001.11:g.94080692del

CM000663.2:g.94080692del

NC_000001.10:g.94546248del

CM000663.1:g.94546248del

NC_000001.9:g.94318836del

NG_009073.1:g.45458del

ENST00000370225.4:c.885del

ENST00000649773.1:c.885del

ENST00000370225.3:c.885del

NM_000350.2:c.885del

Pathogenic

PVS1 PM2_Supporting PS4

Evidence Links 0

Expert Panel

ABCA4 VCEP

Criteria Specification Information

Criteria Specification: ClinGen ABCA4 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCA4 Version 1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ABCA4 VCEP

The NM_000350.3:c.885del (p.Leu296CysfsTer4) variant in ABCA4 is a frameshift variant located in exon 8 of 50 and introduces a premature stop codon between codons 1-2255 (PVS1). The total minor allele frequency in gnomAD v4.1.1 is 0.000008673 (14/1614150 alleles), which is lower than the ClinGen ABCA4 VCEP’s threshold for PM2_Supporting (<0.0001). The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls with an OR of 75.6 and CI of 22.24 to 397.38, which is above the ABCA4 VCEP threshold of ≥5, where the CI does not contain 1 (PS4; PMID: 35120629). In summary, this variant meets the criteria to be classified as pathogenic for ABCA4-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen ABCA4 VCEP (Specification Version 1.0): PVS1, PS4, PM2_Supporting.

PVS1

This is a frameshift variant located in exon 8 out of 50, and introduces a premature stop codon between codons 1-2255 (PVS1).

PM2_Supporting

The total minor allele frequency in gnomAD v4.1.1 is 0.000008673 (14/1614150 alleles), which is lower than the ClinGen ABCA4 VCEP’s threshold for PM2_Supporting (<0.0001), meeting this criterion (PM2_Supporting).

PS4

The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls. The OR is 75.6 and the CI is 22.24 to 397.38, which is above the ABCA4 VCEP threshold of ≥5, where the CI does not contain 1 (PS4; PMID: 35120629).

Curation History

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