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.1988G>A (p.Trp663Ter)

CA16042332

372289 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: 876ff52c-1dd4-4bf0-aa5f-c405e8984d50

Approved on: 2026-07-28

Published on: 2026-08-04

HGVS expressions

NM_000350.3(ABCA4):c.1988G>A (p.Trp663Ter)

NM_000350.3:c.1988G>A

NC_000001.11:g.94060709C>T

CM000663.2:g.94060709C>T

NC_000001.10:g.94526265C>T

CM000663.1:g.94526265C>T

NC_000001.9:g.94298853C>T

NG_009073.1:g.65441G>A

ENST00000370225.4:c.1988G>A

ENST00000649773.1:c.1988G>A

ENST00000370225.3:c.1988G>A

ENST00000472033.1:n.108G>A

ENST00000536513.5:c.-65+2465G>A

NM_000350.2:c.1988G>A

Pathogenic

PS4 PM2_Supporting PVS1

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.1988G>A (p.Trp663Ter) variant in ABCA4 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 14/50 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 v4.1.1 is 0.000001239 (2/1614018 alleles), which is lower than the ClinGen ABCA4 VCEP’s threshold for PM2_Supporting (<0.0001). This variant has been observed in individuals with Stargardt disease and retinal dystrophy (PMID: 25640233, 27353947, 29848554). The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls with an OR of Infinity and CI of 42.77 to 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 (v.1.0.0): PVS1, PS4, PM2_Supporting.

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 42.77 to infinity, which is above the ABCA4 VCEP threshold of ≥5, where the CI does not contain 1 (PS4; PMID: 35120629).

PM2_Supporting

This variant is present in gnomAD v4.1.1 at a total MAF = 0.000001239 (cutoff <0.0001) meeting PM2_Supporting.

PVS1

This is a nonsense variant located in exon 14 out of 50, and introduces a premature stop codon between codons 1-2255 (PVS1).

Curation History

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