CUX1 c.1818A>G, p.Pro606=
NM_001202543.1:c.1818A>G
Variant of Uncertain Significance (VUS)
Using classification after pre-processing (Variant of Uncertain Significance (VUS)) due to LLM failure: LLM response was not valid JSON even after cleaning: Expecting ',' delimiter: line 1 column 10764 (char 10763). Raw response snippet: {"final_classification":"Variant of Uncertain Significance","criteria_evaluation":[{"criterion":"PVS1","is_applied":false,"strength":"Not Applied","justification":"According to standard ACMG guidelines, the rule for PVS1 is: ‘Null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single exon or multiexon deletion) in a gene where loss of function is a known mechanism of disease.’ The evidence for this variant shows it is a synonymous change (P606=) with no alteration of the protein coding sequence. Therefore, this criterion is not applied because the variant is not a null variant."},{"criterion":"PS1","is_applied":false,"strength":"Not Applied","justification":"According to standard ACMG guidelines, the rule for PS1 is: ‘Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.’ The evidence for this variant shows no amino acid change (synonymous). Therefore, this criterion is not applied because there is no am...
ACMG/AMP Criteria Applied
PM2
BP4
Genetic Information
Gene & Transcript Details
Gene
CUX1
Transcript
NM_001202543.1
Total Exons
24
Strand
Forward (+)
Reference Sequence
NC_000007.13
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_001202543.2 | Alternative | 24 exons | Forward |
Variant Details
HGVS Notation
NM_001202543.1:c.1818A>G
Protein Change
P606=
Location
Exon 15
(Exon 15 of 24)
5'Exon Structure (24 total)3'
Functional Consequence
Missense Variant
Related Variants
Variant interpretation based on transcript NM_001202543.1
Genome Browser
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HGVS InputNM_001202543:c.1818A>G
Active Tracks
ConservationRefSeqClinVargnomAD
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Clinical Data
Global Frequency
0.0219%
Low Frequency
Highest in Population
European (non-Finnish)
0.0364%
Low Frequency
Global: 0.0219%
European (non-Finnish): 0.0364%
0%
0.05%
0.1%
1%
5%
10%+
Allele Information
Total: 282860Alt: 62Homozygotes: 0
ACMG Criteria Applied
PM2
This variant is present in gnomAD (MAF= 0.0219%, 62/282860 alleles, homozygotes = 0) and at a higher frequency in the European (non-Finnish) population (MAF= 0.0364%, 47/129164 alleles, homozygotes = 0). The variant is rare (MAF < 0.1%), supporting PM2 criterion application.
Classification
Unknown
Publications (0)
No publication details.
Clinical Statement
Functional Impact
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain (0 mutations).
Related Variants in This Domain
Computational Analysis
Pathogenicity Predictions
Predictor Consensus
Mixed/VUS
PP3 Applied
No
Additional Predictors
Benign:
CADD: 0.48
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PM2
PM2 (Unknown (Pre-LLM)) Strength Modified
From pre-LLM assessment (LLM Failed)
BP4
BP4 (Unknown (Pre-LLM)) Strength Modified
From pre-LLM assessment (LLM Failed)