Variant: NM_001110792.2(MECP2):c.1363G>A (p.Ala455Thr)

CA199489

36491 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

UUID: 94181559-64a8-47c9-8e46-171662a6bbfa

Approved on: 2022-02-18

Published on: 2022-12-02

HGVS expressions

NM_001110792.2:c.1363G>A
NM_001110792.2(MECP2):c.1363G>A (p.Ala455Thr)
NC_000023.11:g.154030501C>T
CM000685.2:g.154030501C>T
NC_000023.10:g.153295952C>T
CM000685.1:g.153295952C>T
NC_000023.9:g.152949146C>T
NG_007107.2:g.111627G>A
NG_007107.3:g.111603G>A
ENST00000303391.11:c.1327G>A
ENST00000453960.7:c.1363G>A
ENST00000303391.10:c.1327G>A
ENST00000453960.6:c.1363G>A
ENST00000619732.4:c.1327G>A
ENST00000628176.2:c.*699G>A
NM_001110792.1:c.1363G>A
NM_001316337.1:c.1048G>A
NM_004992.3:c.1327G>A
NM_001316337.2:c.1048G>A
NM_001369391.2:c.1048G>A
NM_001369392.2:c.1048G>A
NM_001369393.2:c.1048G>A
NM_001369394.1:c.1048G>A
NM_001369394.2:c.1048G>A
NM_001386137.1:c.658G>A
NM_001386138.1:c.658G>A
NM_001386139.1:c.658G>A
NM_004992.4:c.1327G>A

Benign

• Met criteria codes: BS1 BS2

• Not Met criteria codes: PS4

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The allele frequency of the p.Ala443Thr variant in MECP2 (NM_004992.3) is 0.015% in Latino population and 0.014% in East Asian population in gnomAD, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Ala443Thr variant is observed in at least 2 unaffected individuals (RettBASE, PMID 22277191, GeneDx internal database, Invitae internal database) (BS2). In summary, the p.Ala443Thr variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BS1, BS2).

Met criteria codes

• BS1: The allele frequency of the p.Ala443Thr variant in MECP2 is 0.015% in Latino population and 0.014% in East Asian population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions.
• BS2: The p.Ala443Thr variant is observed in at least 2 unaffected individuals (RettBASE, PMID 22277191, GeneDx internal database, Invitae internal database).

Not Met criteria codes

• PS4: RettBASE and PMID 22277191 identified 2 individuals (1 male 1 female) with this variant inherited from phenotypic normal parents, phenotype is not specific for Rett Syndrome, therefore not meeting PS4.