Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001110792.2(MECP2):c.972C>T (p.Val324=)

CA222807

95207 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: e99c40e8-47d2-488a-a7e4-ef2ad06e21bd

Approved on: 2022-05-24

Published on: 2022-06-28

HGVS expressions

NM_001110792.2:c.972C>T

NM_001110792.2(MECP2):c.972C>T (p.Val324=)

NC_000023.11:g.154030892G>A

CM000685.2:g.154030892G>A

NC_000023.10:g.153296343G>A

CM000685.1:g.153296343G>A

NC_000023.9:g.152949537G>A

NG_007107.2:g.111236C>T

NG_007107.3:g.111212C>T

ENST00000303391.11:c.936C>T

ENST00000453960.7:c.972C>T

ENST00000637917.1:n.110C>T

ENST00000303391.10:c.936C>T

ENST00000407218.5:c.*308C>T

ENST00000453960.6:c.972C>T

ENST00000619732.4:c.936C>T

ENST00000622433.4:c.922C>T

ENST00000628176.2:c.*308C>T

NM_001110792.1:c.972C>T

NM_001316337.1:c.657C>T

NM_004992.3:c.936C>T

NM_001316337.2:c.657C>T

NM_001369391.2:c.657C>T

NM_001369392.2:c.657C>T

NM_001369393.2:c.657C>T

NM_001369394.1:c.657C>T

NM_001369394.2:c.657C>T

NM_001386137.1:c.267C>T

NM_001386138.1:c.267C>T

NM_001386139.1:c.267C>T

NM_004992.4:c.936C>T

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"

PM2_Supporting BP4 BP7 BS2_Supporting

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

Computational analysis prediction tools suggest that the p.Val312= variant in MECP2 (NM_004992) does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). The silent p.Val312= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). The p.Val312= variant is observed in at least 1 unaffected individual (GeneDx-internal database) (BS2_Supporting). The p.Val312= variant in MECP2 is absent from gnomAD (PM2_Supporting). In summary, the p.Val312= variant meets the criteria to be classified as Likely Benign. Although there are both pathogenic and benign types of evidence for this variant, the pathogenic evidence is not considered inconsistent with the final classification. ACMG/AMP criteria applied, as specified by the ClinGen Rett/Angelman-like expert panel: (BP4, BP7, BS2_Supporting, PM2_Supporting).

PM2_Supporting

The (p.Val312=) variant in MECP2 is absent from gnomAD (PM2_Supporting)

BP4

Computational analysis prediction tools suggest that the p.(Val312=) variant does not have a deleterious impact; however this information does not predict clinical significance on its own

BP7

The silent p.(Val312=) variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide

BS2_Supporting

The p.Val312= variant is observed in at least 1unaffected individuals (GeneDx internal case)

Curation History

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