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_000330.4:c.52+2T>A

CA412378903

Gene: RS1 (HGNC:6247)

Condition: X-linked retinoschisis (MONDO:0010725)

Inheritance Mode: X-linked inheritance

UUID: d91e17a5-2824-4d5c-b3de-ac7d49bf1de3

Approved on: 2026-09-26

Published on: 2026-09-26

HGVS expressions

NM_000330.4:c.52+2T>A

NC_000023.11:g.18672015A>T

CM000685.2:g.18672015A>T

NC_000023.10:g.18690135A>T

CM000685.1:g.18690135A>T

NC_000023.9:g.18600056A>T

NG_008659.3:g.10434T>A

ENST00000379984.4:c.52+2T>A

ENST00000379984.3:c.52+2T>A

NM_000330.3:c.52+2T>A

Pathogenic

PP4 PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

X-linked Inherited Retinal Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RS1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

The NM_000330.4(RS1):c.52+2T>A variant is a canonical splice site variant in intron 1, located 2 nucleotides after exon 1. This variant occurs at a canonical splice site in intron 1 and is predicted to disrupt splicing and induce skipping of exon 2, which is expected to introduce a premature stop codon and disrupt a critical functional domain in RS1 (PVS1). This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting). At least one proband harboring this variant exhibits the following phenotypes, including the appearance of schisis and reduced visual acuity before age 13 years, which together are specific for X-linked retinoschisis (PMID: 33124204, PP4). In summary, this variant is classified as pathogenic for X-linked retinoschisis based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RS1 Version 1.0.0: PVS1, PM2_Supporting, and PP4.

PP4

At least one proband harboring this variant exhibits the following phenotypes, including the appearance of schisis and reduced visual acuity before age 13 years, which together are specific for X-linked retinoschisis (PMID: 33124204, PP4).

PVS1

This variant occurs at a canonical splice site in intron 1 and is predicted to disrupt splicing and induce skipping of exon 2, which is expected to introduce a premature stop codon and disrupt a critical functional domain in RS1 (PVS1).

PM2_Supporting

This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting).

Curation History

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