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

Variant: NM_000419.5(ITGA2B):c.2449-11C>T

CA8602674

888827 (ClinVar)

Gene: ITGA2B
Condition: Glanzmann thrombasthenia
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 998491e4-373b-4b98-bf60-06f760a0f7d0
Approved on: 2025-03-06
Published on: 2025-03-06

HGVS expressions

NM_000419.5:c.2449-11C>T
NM_000419.5(ITGA2B):c.2449-11C>T
NC_000017.11:g.44375996G>A
CM000679.2:g.44375996G>A
NC_000017.10:g.42453364G>A
CM000679.1:g.42453364G>A
NC_000017.9:g.39808890G>A
NG_008331.1:g.18510C>T
ENST00000262407.6:c.2449-11C>T
ENST00000648408.1:c.1880-11C>T
ENST00000262407.5:c.2449-11C>T
ENST00000587295.5:c.101-11C>T
ENST00000592462.5:n.1244-11C>T
NM_000419.3:c.2449-11C>T
NM_000419.4:c.2449-11C>T
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Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 4
PP4 BA1 PM2 BS1

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 NM_000419.5(ITGA2B):c.2449-11C>T variant is a intronic variant variant that is not predicted by SpliceAI to impact splicing and the nucleotide is only moderately conserved, as shown by phyloP score of 1.044 (BP4, BP7). The highest population minor allele frequency in gnomAD v3.1.2 is 0.0007726 (32/41418 alleles) in the African/African American population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting so no allele frequency criteria were met. In addition, no cases of the variant segregating with Glanzmann thrombasthenia were found in the literature. In summary, this variant meets the criteria to be classified as likely benign for autosomal recessive Glanzmann Thrombasthenia with the following ACMG/AMP applied, as specified by the ClinGen PD VCEP: BP4, BP7 (VCEP specifications version 2.1)
Met criteria codes
BP4
intronic variant that is not predicted by SpliceAI to impact splicing (delta scores <=0.03)
BP7
The NM_000419.5(ITGA2B):c.2449-11C>T variant is a intronic variant that is not predicted by SpliceAI to impact splicing (delta scores <=0.03) and the nucleotide is only moderately conserved, as shown by phyloP score of 1.044.
Not Met criteria codes
PP4
This variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population, however, no cases of the variant segregating with GT were found in the literature.
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest population minor allele frequency in gnomAD v4 is 0.0009597 (72/75020 alleles) in the African/African American population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting.
BS1
The highest population minor allele frequency in gnomAD v4 is 0.0009597 (72/75020 alleles) in the African/African American population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting.
Curation History
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