SH2B3 c.784T>C, p.Trp262Arg
NM_005475.2:c.784T>C
COSM4985153
Population Frequency
66.8%
Common
ClinVar Classification
Benign
0 publications
REVEL Score
0.172
Likely Benign
COSMIC Recurrence
28 occurrences
PM1 Criterion Applied
Classification Evidence
Detailed Information
Genetic Information
Gene & Transcript Details
Gene
SH2B3
Transcript
NM_005475.3
MANE Select
Total Exons
8
Strand
Forward (+)
Reference Sequence
NC_000012.11
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_005475.2 | RefSeq Select | 8 exons | Forward |
| NM_005475.1 | Alternative | 8 exons | Forward |
Variant Details
HGVS Notation
NM_005475.2:c.784T>C
Protein Change
W262R
Location
Exon 3
(Exon 3 of 8)
5'
Exon Structure (8 total)
3'
Functional Consequence
Missense Variant
Related Variants
No evidence of other pathogenic variants at position 262 in gene SH2B3
Alternate Identifiers
COSM4985153
Variant interpretation based on transcript NM_005475.3
Clinical Evidence
Global Frequency
66.8%
Common
Highest in Population
East Asian
99.9%
Common
Global: 66.8%
East Asian: 99.9%
0%
0.0005%
0.001%
0.01%
0.05%
1%+
Allele Information
Total: 251784
Alt: 168200
Homozygotes: 60933
ACMG Criteria Applied
BA1
This variant is common in the population (66.800000% MAF).
Classification
Benign
Based on 3 submitter reviews in ClinVar
Submitter Breakdown
Pathogenic
Likely Pathogenic
VUS
Likely Benign
Benign
Publications
0 publications
Clinical Statement
This variant has been reported in ClinVar as Benign (3 clinical laboratories).
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 262 in gene SH2B3
Functional Studies
Summary
The variant SH2B3 W262R has not been functionally characterized in the provided sources.
Computational Evidence
Pathogenicity Predictions
REVEL Score
0.172
0.172
Likely Benign
0.0
Uncertain (Low)
0.2
Uncertain (Med)
0.5
Likely Pathogenic
0.75
REVEL scores ≥ 0.75 are considered strong evidence of pathogenicity (PP3)
Predictor Consensus
Unknown
PP3 Applied
No
VCEP Guidelines
Applied ACMG/AMP Criteria
BP4
BP4 (Supporting)
According to standard ACMG guidelines: 'Multiple lines of computational evidence suggest no impact.' The evidence for this variant shows: Insufficient in silico prediction data; SpliceAI predicts no impact on splicing. Therefore, this criterion meets the requirements because the computational evidence indicates a lack of deleterious effect.
BP6
BP6 (Supporting)
According to standard ACMG guidelines: 'Reputable source reports variant as benign, but without accessible evidence.' The evidence for this variant shows: This variant has been reported in ClinVar as Benign by 3 clinical laboratories. Therefore, this criterion meets the requirements because it is supported by multiple reputable sources.
BA1
BA1 (Strong)
Strength Modified
According to standard ACMG guidelines: 'Allele frequency is too high for the disorder.' The evidence for this variant shows: MAF = 66.8% in gnomAD, indicating it is common and not consistent with a pathogenic variant. Therefore, this criterion meets the requirements because the allele frequency is significantly higher than expected for a pathogenic variant.