Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001110792.2(MECP2):c.1216_1251del (p.Glu406_Pro417del)

CA10558461

393491 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: fdc90840-663d-4a00-b984-1e5fdd8221ed
Approved on: 2024-10-30
Published on: 2024-11-29

HGVS expressions

NM_001110792.2:c.1216_1251del
NM_001110792.2(MECP2):c.1216_1251del (p.Glu406_Pro417del)
NC_000023.11:g.154030622_154030657del
CM000685.2:g.154030622_154030657del
NC_000023.10:g.153296073_153296108del
CM000685.1:g.153296073_153296108del
NC_000023.9:g.152949267_152949302del
NG_007107.2:g.111480_111515del
NG_007107.3:g.111456_111491del
ENST00000303391.11:c.1180_1215del
ENST00000453960.7:c.1216_1251del
ENST00000303391.10:c.1180_1215del
ENST00000407218.5:c.*552_*587del
ENST00000453960.6:c.1216_1251del
ENST00000619732.4:c.1180_1215del
ENST00000628176.2:c.*552_*587del
NM_001110792.1:c.1216_1251del
NM_001316337.1:c.901_936del
NM_004992.3:c.1180_1215del
NM_001316337.2:c.901_936del
NM_001369391.2:c.901_936del
NM_001369392.2:c.901_936del
NM_001369393.2:c.901_936del
NM_001369394.1:c.901_936del
NM_001369394.2:c.901_936del
NM_001386137.1:c.511_546del
NM_001386138.1:c.511_546del
NM_001386139.1:c.511_546del
NM_004992.4:c.1180_1215del
More

Likely Benign

Met criteria codes 2
BS2 BP5
Not Met criteria codes 3
BS1 PM6 PM4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MECP2 Version 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Glu394_Pro405del variant in MECP2 (NM_004992.4) is observed in at least 20 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2). The p.Glu394_Pro405del variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - GeneDx; internal database - Invitae) (BP5). The highest population minor allele frequency of the p.Glu394_Pro405del variant in MECP2 in gnomAD v4.1 is 0.00003691 in European (non-Finnish) population (not sufficient to meet BS1 criteria). In summary, the p.Glu394_Pro405del variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP5).
Met criteria codes
BS2
The p.Glu394_Pro405del variant is observed in at least 20 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2).
BP5
The p.Glu394_Pro405del variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - GeneDx; internal database - Invitae) (BP5).
Not Met criteria codes
BS1
The highest population minor allele frequency of the p.Glu394_Pro405del variant in MECP2 in gnomAD v4.1 is 0.00003691 in European (non-Finnish) population (not sufficient to meet BS1 criteria).
PM6
The p.Glu394_Pro405del variant in MECP2 (NM_004992.4) has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with a neurodevelopmental disorder (internal database - GeneDx). This variant is seen in multiple unaffected adults based on internal lab data from GeneDx and Invitae (at least 20 unaffected individuals) and although the variant does not meet BS1, it is present in multiple individuals in gnomAD v4.1 including 15 XY individuals. Given the high frequency of the variant in unaffected individuals, we are not counting PM6 based on the unconfirmed de novo from GeneDx. This is unpublished internal lab data and is confounding evidence that we are not putting weight on. Therefore, for clarity reasons we are not counting PM6 and will not mention this in the summary.
PM4
Variant is in the proline-rich region p.381-p.405
Curation History
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