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_000212.3:c.1125+3_1125+6del

CA291225439

996205 (ClinVar)

Gene: ITGB3
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 8a8e75a9-8380-452b-aecb-047b372dd08f
Approved on: 2024-03-07
Published on: 2024-03-08

HGVS expressions

NM_000212.3:c.1125+3_1125+6del
NC_000017.11:g.47290277_47290280del
CM000679.2:g.47290277_47290280del
NC_000017.10:g.45367643_45367646del
CM000679.1:g.45367643_45367646del
NC_000017.9:g.42722642_42722645del
NG_008332.2:g.41436_41439del
ENST00000696963.1:c.1125+3_1125+6del
ENST00000559488.7:c.1125+3_1125+6del
ENST00000559488.5:c.1125+3_1125+6del
ENST00000560629.1:c.1090+3_1090+6del
ENST00000571680.1:c.1125+3_1125+6del
NM_000212.2:c.1125+3_1125+6del
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Uncertain Significance

Met criteria codes 2
PP3 PM2_Supporting
Not Met criteria codes 2
PP4 PM3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2.1

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Platelet Disorders VCEP
The ITGB3 splice donor region variant NM_000212.3:c.1125+3_1125+6del located at the 3' end of exon 8/5' end of intron 8 is predicted by multiple in silico splicing tools, including SpliceAI, to disrupt the canonical splice donor site (PP3). This variant has been observed in heterozygosity in an individual suspected to have Glanzmann's thrombasthenia (GT) (CabGT-25 in PMID: 20020534), however sufficient information to confirm if the individual's phenotype is specific for GT was not provided and a second ITGB3 variant was not identified. The variant is also absent from control population databases, including gnomADv4.0. In summary, this variant is of uncertain significance and lacks sufficient evidence to be classified as pathogenic or benign for GT. GT-specific criteria applied: PM2_supporting, PP3.
Met criteria codes
PP3
Multiple in silico splice tools predict this variant leads to loss of the canonical splice donor: SpliceAI (Δ score = 1), MaxEntScan (-140.518% change in score between wild type and variant), NNSPLICE (wild type donor site score =1, variant donor site not recognized).
PM2_Supporting
This is a rare variant not reported in control population databases, including gnomAD v4.0, meeting the criterion to apply PM2_supporting.
Not Met criteria codes
PP4
This variant was reported in heterozygosity in one individual (CabGT-25, PMID: 20020534), however sufficient phenotypic information (bleeding phenotype, surface protein expression, platelet aggregation) to meet PP4 were not provided.
PM3
This variant was reported in heterozygosity in one individual (CabGT-25 in PMID: 20020534), however a second ITGB3 variant was not identified.
Curation History
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