Variant: NM_004992.3(MECP2):c.1140G>A (p.Val380=)

CA208360

138194 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

UUID: 7277ad9e-b07e-4eeb-a2db-80b1b1fe619f

HGVS expressions

NM_004992.3:c.1140G>A
NM_004992.3(MECP2):c.1140G>A (p.Val380=)
ENST00000303391.11:c.1140G>A
ENST00000453960.7:c.1176G>A
ENST00000303391.10:c.1140G>A
ENST00000407218.5:c.*512G>A
ENST00000453960.6:c.1176G>A
ENST00000619732.4:c.1140G>A
ENST00000628176.2:c.*512G>A
NM_001110792.1:c.1176G>A
NM_001316337.1:c.861G>A
NM_001110792.2:c.1176G>A
NM_001316337.2:c.861G>A
NM_001369391.2:c.861G>A
NM_001369392.2:c.861G>A
NM_001369393.2:c.861G>A
NM_001369394.1:c.861G>A
NM_001369394.2:c.861G>A
NM_001386137.1:c.471G>A
NM_001386138.1:c.471G>A
NM_001386139.1:c.471G>A
NM_004992.4:c.1140G>A
NC_000023.11:g.154030688C>T
CM000685.2:g.154030688C>T
NC_000023.10:g.153296139C>T
CM000685.1:g.153296139C>T
NC_000023.9:g.152949333C>T
NG_007107.2:g.111440G>A
NG_007107.3:g.111416G>A

Benign

• Met criteria codes: BS2 BS1 BP7

• Not Met criteria codes: BA1

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.Val380= variant in MECP2 is 0.018% in Latino sub 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 (BS1). The p.Val380= variant is observed in at least 2 unaffected individuals (internal database) (BS2). The silent p.Val380= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Val380= variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP7).

Met criteria codes

• BS2: The p.Val380= variant is observed in at least 2 unaffected individuals (internal database)
• BS1: The allele frequency of the p.Val380= variant in MECP2 is 0.018% in Latino sub 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
• BP7: The silent p.Val380= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide

Not Met criteria codes

• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2021-03-26

Published on: 2021-05-17