Vitelliform macular dystrophy 2: genes and variants

Genes linked to Vitelliform macular dystrophy 2

• BEST1: Bestrophin-1

  It helps regulate ion transport and fluid homeostasis across the retinal pigment epithelium. Pathogenic variants cause bestrophinopathies including Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, and some retinitis pigmentosa phenotypes.

  39 disease-causing and 25 uncertain variants in BEST1 are linked to Vitelliform macular dystrophy 2.

• PRPH2: Peripherin-2

  It organizes and stabilizes the rim structure of photoreceptor outer-segment discs. Pathogenic variants cause a wide range of inherited retinal diseases including retinitis pigmentosa, pattern dystrophy, and macular dystrophy.

  3 disease-causing and 6 uncertain variants in PRPH2 are linked to Vitelliform macular dystrophy 2.

Where Vitelliform macular dystrophy 2 variants cluster

• BEST1 Cytoplasmic (positions 1–31): 11 of 39 disease-causing changes, 5.3× more than its size predicts.
• BEST1 Transmembrane (positions 238–255): 3 of 39 disease-causing changes, 2.5× more than its size predicts.

Known disease-causing variants in Vitelliform macular dystrophy 2

Which prediction tools work for Vitelliform macular dystrophy 2

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• PolyPhen-2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 90 out of 100
• CADD: 88 out of 100
• phyloP: 68 out of 100

Same protein, different disease

• Autosomal recessive bestrophinopathy is also caused by BEST1 variants; they fall mostly in different places as the Vitelliform macular dystrophy 2 variants (22 disease-causing).
• Autosomal dominant vitreoretinochoroidopathy is also caused by BEST1 variants; they fall mostly in different places as the Vitelliform macular dystrophy 2 variants (9 disease-causing).
• Retinal disorder is also caused by BEST1 variants; they fall in the same places as the Vitelliform macular dystrophy 2 variants (4 disease-causing).
• BEST1-related dominant retinopathy is also caused by BEST1 variants; they fall mostly in different places as the Vitelliform macular dystrophy 2 variants (3 disease-causing).
• Retinitis pigmentosa is also caused by PRPH2 variants; they fall partly in the same places as the Vitelliform macular dystrophy 2 variants (14 disease-causing).
• Patterned dystrophy of the retinal pigment epithelium is also caused by PRPH2 variants; they fall mostly in different places as the Vitelliform macular dystrophy 2 variants (11 disease-causing).
• Stargardt disease is also caused by PRPH2 variants; they fall mostly in different places as the Vitelliform macular dystrophy 2 variants (4 disease-causing).
• Pigmentary retinal dystrophy is also caused by PRPH2 variants; they fall mostly in different places as the Vitelliform macular dystrophy 2 variants (3 disease-causing).
• Patterned macular dystrophy 1 is also caused by PRPH2 variants; they fall mostly in different places as the Vitelliform macular dystrophy 2 variants (3 disease-causing).

Diseases related to Vitelliform macular dystrophy 2

• Retinitis pigmentosa, also linked to BEST1 and PRPH2
• Retinal disorder, also linked to BEST1 and PRPH2
• Stargardt disease, also linked to PRPH2
• Cone-rod dystrophy, also linked to PRPH2
• Autosomal recessive bestrophinopathy, also linked to BEST1
• Patterned dystrophy of the retinal pigment epithelium, also linked to PRPH2
• Autosomal dominant vitreoretinochoroidopathy, also linked to BEST1
• Pigmentary retinal dystrophy, also linked to PRPH2
• Isolated macular dystrophy, also linked to BEST1
• Patterned macular dystrophy 1, also linked to PRPH2
• BEST1-related dominant retinopathy, also linked to BEST1
• Choroidal dystrophy, central areolar 2, also linked to PRPH2

Frequently asked questions

Which genes are linked to Vitelliform macular dystrophy 2?

In CATVariant, Vitelliform macular dystrophy 2 is linked to 2 analyzed proteins: BEST1 (Bestrophin-1) and PRPH2 (Peripherin-2).

How many genetic variants are linked to Vitelliform macular dystrophy 2?

164 variants: 42 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 31 are of uncertain significance or have conflicting reports.

Which uncertain variants in Vitelliform macular dystrophy 2 look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Vitelliform macular dystrophy 2?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.90, based on 39 disease-causing and 10 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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