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(ABCA4):c.6601_6602del (p.Arg2201fs)

CA227421

99472 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: 9999a507-2664-439d-b776-c994e5d920cb

Approved on: 2026-02-24

Published on: 2026-02-27

HGVS expressions

NM_000350.3(ABCA4):c.6601_6602del (p.Arg2201fs)

NM_000350.3:c.6601_6602del

NC_000001.11:g.93997991_93997992del

CM000663.2:g.93997991_93997992del

NC_000001.10:g.94463547_94463548del

CM000663.1:g.94463547_94463548del

NC_000001.9:g.94236135_94236136del

NG_009073.1:g.128161_128162del

ENST00000370225.4:c.6601_6602del

ENST00000370225.3:c.6601_6602del

ENST00000536513.5:c.2977_2978del

NM_000350.2:c.6601_6602del

Pathogenic

PVS1 PS4 PM2_Supporting

PP1 PP4

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 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ABCA4 VCEP

The NM_000350.3:c.6601_6602del (p.Arg2201AlafsTer) variant in ABCA4 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 48/50 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The total minor allele frequency in gnomAD v4.1.0 is 0.0000006196 (1/1614010 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. The OR is infinity and the CI is 2.24-infinity, 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 1.0.0): PVS1, PS4, PM2_Supporting.

PVS1

This is a frameshift variant located in exon 48 out of 50, and introduces a premature stop codon between codons 1-2255 (PVS1).

PS4

The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls. The OR is infinity and the CI is 2.24-infinity, which is above the ABCA4 VCEP threshold of ≥5, where the CI does not contain 1 (PS4; PMID: 35120629).

PM2_Supporting

The total minor allele frequency in gnomAD v4.1.0 is 0.0000006196 (1/1614010 alleles), which is lower than the ClinGen ABCA4 VCEP’s threshold for PM2_Supporting (<0.0001), meeting this criterion (PM2_Supporting).

PP1

This variant segregates in 2 family members (siblings), but they do not appear to be affected based on the pedigree.

PP4

This variant has been reported in the literature in several individuals with ABCA4-related retinopathy, but none with phenotypes that meet the requirements of the PP4 code as specified by the ClinGen ABCA4 VCEP (PMIDs: 34440443, 32307445, 20647261, 10958761, 12037008).

Curation History

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