17-44381058-A-G
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PP1_ModeratePM2_SupportingPP4_StrongPM3_Strong
This summary comes from the ClinGen Evidence Repository: The c.1214T>C (p.Ile405Thr) variant has been reported in at least four compound heterozygous probands (PMIDs: 12424194, 12083483, 24418945, 25728920) with a phenotype highly specific to GT. In one case the variant cosegregated with disease in the proband and two siblings (PMID:12424194). It is absent from Exac and gnomAD. In summary, this variant meets criteria to be classified as Pathogenic for GT. GT-specific criteria applied: PM3_Strong, PM2_Supporting, PP1_Moderate, PP3 and PP4_Strong. LINK:https://erepo.genome.network/evrepo/ui/classification/CA290950815/MONDO:0010119/011
Frequency
Consequence
NM_000419.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITGA2B | NM_000419.5 | c.1214T>C | p.Ile405Thr | missense_variant | Exon 13 of 30 | ENST00000262407.6 | NP_000410.2 | |
ITGA2B | XM_011524749.2 | c.1367T>C | p.Ile456Thr | missense_variant | Exon 13 of 29 | XP_011523051.2 | ||
ITGA2B | XM_011524750.2 | c.1367T>C | p.Ile456Thr | missense_variant | Exon 13 of 29 | XP_011523052.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITGA2B | ENST00000262407.6 | c.1214T>C | p.Ile405Thr | missense_variant | Exon 13 of 30 | 1 | NM_000419.5 | ENSP00000262407.5 | ||
ITGA2B | ENST00000648408.1 | c.644T>C | p.Ile215Thr | missense_variant | Exon 9 of 25 | ENSP00000498119.1 | ||||
ITGA2B | ENST00000592226.5 | n.454T>C | non_coding_transcript_exon_variant | Exon 7 of 10 | 5 | |||||
ITGA2B | ENST00000592462.5 | n.9T>C | non_coding_transcript_exon_variant | Exon 2 of 15 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461000Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726730
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Glanzmann thrombasthenia Pathogenic:1
The c.1214T>C (p.Ile405Thr) variant has been reported in at least four compound heterozygous probands (PMIDs: 12424194, 12083483, 24418945, 25728920) with a phenotype highly specific to GT. In one case the variant cosegregated with disease in the proband and two siblings (PMID: 12424194). It is absent from Exac and gnomAD. In summary, this variant meets criteria to be classified as Pathogenic for GT. GT-specific criteria applied: PM3_Strong, PM2_Supporting, PP1_Moderate, PP3 and PP4_Strong. -
Glanzmann thrombasthenia 1 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at