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.5917del (p.Gly1972_Val1973insTer)

CA227355

99419 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: 637cbdd5-017d-4c22-90d6-8cc2d4c9f77c

Approved on: 2026-07-28

Published on: 2026-07-28

HGVS expressions

NM_000350.3(ABCA4):c.5917del (p.Gly1972_Val1973insTer)

NM_000350.3:c.5917del

NC_000001.11:g.94007722del

CM000663.2:g.94007722del

NC_000001.10:g.94473278del

CM000663.1:g.94473278del

NC_000001.9:g.94245866del

NG_009073.1:g.118428del

ENST00000370225.4:c.5917del

ENST00000370225.3:c.5917del

ENST00000465352.1:n.333del

ENST00000484388.1:n.31del

ENST00000536513.5:c.2293del

NM_000350.2:c.5917del

Pathogenic

PM2_Supporting PVS1 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(ABCA4):c.5917del; p.Val1973Ter variant in ABCA4 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 43 of 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 0.00001363 (22/1613736 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 537.2 and CI is 145.66 to 5177.53, 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.

PM2_Supporting

The total minor allele frequency in gnomAD v4.1.0 is 0.00001363 (22/1613736 alleles), which is lower than the ClinGen ABCA4 VCEP’s threshold for PM2_Supporting (<0.0001), meeting this criterion (PM2_Supporting).

PVS1

This is a frameshift variant located in exon 43 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 537.2 and the CI is 145.66 to 5177.53, 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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