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
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  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000330.4(RS1):c.185-3137C>A

CA10360734

434667 (ClinVar)

Gene: CDKL5
Condition: CDKL5 disorder
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 909bf950-9b44-4c93-abb5-60d97cd8cdc5
Approved on: 2023-02-20
Published on: 2023-06-02

HGVS expressions

NM_000330.4:c.185-3137C>A
NM_000330.4(RS1):c.185-3137C>A
NC_000023.11:g.18650469G>T
CM000685.2:g.18650469G>T
NC_000023.10:g.18668589G>T
CM000685.1:g.18668589G>T
NC_000023.9:g.18578510G>T
NG_008475.1:g.229865G>T
NG_008659.3:g.31980C>A
ENST00000379984.4:c.185-3137C>A
ENST00000673617.1:n.129G>T
ENST00000379984.3:c.185-3137C>A
ENST00000379989.6:c.2857G>T
ENST00000379996.7:c.2857G>T
ENST00000476595.1:n.69C>A
NM_000330.3:c.185-3137C>A
NM_001037343.1:c.2857G>T
NM_003159.2:c.2857G>T
NM_001037343.2:c.2857G>T
NM_003159.3:c.2857G>T
More

Likely Benign

Met criteria codes 2
BP5 BP4
Not Met criteria codes 3
BS1 PM2 PM1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
RS1(NM_000330.4) and an alternative transcript of CDKL5 (NM_003159.2) are overlapping transcripts; however, these variants are in the noncoding 3' region of the main CDKL5 transcript (NM_001323289.2). The c.2857G>T (p.Ala953Ser) variant in CDKL5 transcript (NM_003159.2) (RS1 c.185-3137C>A) is present in 2 male individuals in gnomAD (0.002%) (not sufficient to meet BS1 criteria). The p.Ala953Ser variant is found in a patient with an alternate molecular basis of disease (internal database - Invitae) (BP5). Additionally, computational analysis prediction tools suggest that the p.Ala953Ser variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Ala953Ser variant in CDKL5 (NM_003159.2) is classified as likely benign based on the ACMG/AMP criteria (BP5, BP4).
Met criteria codes
BP5
The p.Ala953Ser variant is found in a patient with an alternate molecular basis of disease (internal database - Invitae).
BP4
Computational analysis prediction tools suggest that the p.Ala953Ser variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4).
Not Met criteria codes
BS1
The p.Ala953Ser variant in CDKL5 is present in 2 male individuals in gnomAD (0.002%) (not sufficient to meet BS1 criteria).
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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