STAG2 c.1240dupT, p.Tyr414LeufsTer27

NM_001042749.1:c.1240dupT
COSMIC ID: COSM6964604
Likely Pathogenic
The final classification of NM_001042749.1:c.1240dupT in the STAG2 gene is Likely Pathogenic. This classification is supported by the application of PVS1 due to the truncating nature of the variant and PM2 due to its absence in population databases, indicating it is not a common benign variant.
ACMG/AMP Criteria Applied
PVS1 PM2

Genetic Information

Gene & Transcript Details
Gene
STAG2
Transcript
NM_001042749.2
Total Exons
35
Strand
Forward (+)
Reference Sequence
NC_000023.10
Alternative Transcripts
IDStatusDetails
NM_001042749.1 Alternative 35 exons | Forward
Variant Details
HGVS Notation
NM_001042749.1:c.1240dupT
Protein Change
Y414Lfs*27
Location
Exon 14 (Exon 14 of 35)
14
5'Exon Structure (35 total)3'
Functional Consequence
Loss of Function
Related Variants
No evidence of other pathogenic variants at position 414 in gene STAG2
Alternate Identifiers
COSM6964604
Variant interpretation based on transcript NM_001042749.2

Genome Browser

UCSC Genome Browser hg19/GRCh37
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HGVS InputNM_001042749:c.1240dupT
Active Tracks
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Clinical Data

Population Frequency
Global Frequency
0.0 in 100,000
Extremely Rare
Global: 0.0%
0%
0.05%
0.1%
1%
5%
10%+
ACMG Criteria Applied
PM2
This variant is rare in the population (0.000000% MAF).
ClinVar 2025-04-08T12:10:34.143357
Classification
Unknown
Publications (0)
No publication details.
Clinical Statement
COSMIC
COSMIC ID
COSM6964604
Recurrence
1 occurrences
PM1 Criteria
Not Applied
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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
No evidence of other pathogenic variants at position 414 in gene STAG2
Functional Studies & Therapeutic Relevance
Functional Summary
The variant STAG2 Y414Lfs*27 has not been functionally characterized in the provided sources.

Computational Analysis

Pathogenicity Predictions
Predictor Consensus
Unknown
PP3 Applied
No
SpliceAI Scores Window: ±500bp
Effect TypeScorePosition
-Acceptor Loss
0.0
-42 bp
-Donor Loss
0.0
68 bp
+Acceptor Gain
0.01
20 bp
+Donor Gain
0.0
67 bp
High impact (≥0.5)
Medium impact (0.2-0.49)
Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)
PVS1
PVS1 (Very Strong)
According to VCEP guidelines: 'PVS1 – Null variant in a gene where loss of function (LoF) is a known mechanism of disease.' The evidence for this variant shows: It is a truncating variant (Y414Lfs*27) in the STAG2 gene, where loss of function is a known mechanism of disease. Therefore, this criterion meets the requirements because the variant is predicted to result in a loss of function.
PM2
PM2 (Moderate)
According to VCEP guidelines: 'PM2 – Absent from controls (or at extremely low frequency if recessive).' The evidence for this variant shows: The variant is not found in population databases such as gnomAD, indicating it is absent from controls. Therefore, this criterion meets the requirements because the variant is not present in the general population.