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Table 2 Classification of uncertain cases suspected of having ADNP syndrome

From: Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome

ID ADNP variant In silico assessment d Population allele frequency (%)e Classification (score) Support for prediction
ADNP_18 a Not known N/A N/A ADNP-2 (0.90) f
ADNP_26 b c.201G>C (p.Gln67His) Deleterious 0 ADNP-1 (0.95) g
ADNP_01 b c.1039A>G (p.Met347Val) Tolerated 0.008 None (0.96) h
ADNP_06 b c.2963C>T (p.Thr988Ile) Conflicting 0.0004 None (0.97) h, i
ADNP_19 b c.356A>G (p.Lys119Arg) Conflicting 0.007 None (0.96) h
ADNP_27 b, c c.1855G>T (p.Val619Phe) Deleterious 0.003 None (0.95) h, j
ADNP_28 b, c c.1855G>T (p.Val619Phe) Deleterious 0.003 None (0.95) h, j
  1. aThis patient was a confirmed case of ADNP syndrome, but the mutation was not known at the time of the study. bReason for assessment was reporting of a variant of unknown clinical significance in ADNP. cSubjects ADNP_27 and ADNP_28 are fraternal twins sharing a missense change with an unknown mode of inheritance. dIn Silico assessment for the suspected variant was performed using three tools: SIFT, PolyPhen, and MutationTaster. A “tolerated” or “deleterious” decision was assigned only if all three tools were in agreement with regard to the variant. eAllele frequency was obtained from the gnomAD database (v2.1) and represents the combined frequencies of different subpopulations; fADNP sequencing later identified a nonsense variant in the expected ADNP-2 region: c.2156dupA (p.Tyr719*). gVariant is absent from the general population and was classified as likely pathogenic according to the ACMG guidelines. hPopulation minor allele frequency is too high for a dominant condition. iVariant is inherited from an unaffected mother. jNo further data is available for assessment. N/A not applicable. ADNP transcript, NM_015339.4. Photographs of some of these subjects are provided in Additional file 1: Figure S1