Variant: NM_001110792.2(MECP2):c.1490_1493del (p.Val497fs)

CA273848

143485 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

UUID: 59542a41-0c1c-47cb-8ce1-4e85f89f2ae4

HGVS expressions

NM_001110792.2:c.1490_1493del
NM_001110792.2(MECP2):c.1490_1493del (p.Val497fs)
NC_000023.11:g.154030373_154030376del
CM000685.2:g.154030373_154030376del
NC_000023.10:g.153295824_153295827del
CM000685.1:g.153295824_153295827del
NC_000023.9:g.152949018_152949021del
NG_007107.2:g.111754_111757del
NG_007107.3:g.111730_111733del
ENST00000303391.11:c.1454_1457del
ENST00000453960.7:c.1490_1493del
ENST00000303391.10:c.1454_1457del
ENST00000453960.6:c.1490_1493del
ENST00000619732.4:c.1450_1453del
ENST00000628176.2:c.*826_*829del
NM_001110792.1:c.1490_1493del
NM_001316337.1:c.1175_1178del
NM_004992.3:c.1454_1457del
NM_001316337.2:c.1175_1178del
NM_001369391.2:c.1175_1178del
NM_001369392.2:c.1175_1178del
NM_001369393.2:c.1175_1178del
NM_001369394.1:c.1175_1178del
NM_001369394.2:c.1175_1178del
NM_001386137.1:c.785_788del
NM_001386138.1:c.785_788del
NM_001386139.1:c.785_788del
NM_004992.4:c.1454_1457del

Pathogenic

• Met criteria codes: PM6_Strong PVS1 PS4_Moderate PM2_Supporting PP4

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Val485fs (NM_004992) variant in MECP2 is predicted to cause a frameshift that results in a read-through of the stop codon (PVS1). The p.Val485fs variant in MECP2 has been reported as de novo occurrence in at least two individuals (biological parentage unconfirmed) with Rett Syndrome (PMID 11402105, Clinvar Variation ID: 143485) (PM6_strong). The p.Val485fs variant has been observed in at least 3 other individuals with Rett Syndrome (PMID 11402105, PMID 16473305, ClinVar) (PS4_moderate). The p.Val485fs variant in MECP2 is absent from gnomAD (PM2_supporting). The p.Val485fs variant in MECP2 has been reported in an individual with a clinical phenotype suggestive of Rett Syndrome (PMID 11402105) (PP4). In summary the p.Val485fs variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PVS1, PM6_strong, PS4_moderate, PM2_supporting, PP4).

Met criteria codes

• PM6_Strong: PM6_strong:The p.Val485fs variant in MECP2 has been reported as de novo occurrence in at least two individuals (biological parentage unconfirmed) with Rett Syndrome (PMID 11402105),Clinvar Variation ID: 143485.
• PVS1: The p.Val485fs variant in MECP2 is predicted to cause a frameshift that results in a read-through of the stop codon.
• PS4_Moderate: PS4_moderate:The p.Val485fs variant has been observed in at least 3 other individuals with Rett Syndrome(PMID 11402105, PMID 16473305, ClinVar)
• PM2_Supporting: PM2_supporting:The p.Val485fs variant in MECP2 is absent from gnomAD
• PP4: PP4.The p.Val485fs variant in MECP2 has been reported in an individual with a clinical phenotype suggestive of Rett Syndrome ( PMID 11402105)

Approved on: 2022-05-10

Published on: 2022-06-28