rs75028796
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000419.5(ITGA2B):c.1913dupT(p.Cys639MetfsTer22) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000192 in 1,560,796 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000419.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITGA2B | NM_000419.5 | c.1913dupT | p.Cys639MetfsTer22 | frameshift_variant | Exon 19 of 30 | ENST00000262407.6 | NP_000410.2 | |
ITGA2B | XM_011524749.2 | c.2066dupT | p.Cys690MetfsTer22 | frameshift_variant | Exon 19 of 29 | XP_011523051.2 | ||
ITGA2B | XM_011524750.2 | c.2066dupT | p.Cys690MetfsTer22 | frameshift_variant | Exon 19 of 29 | XP_011523052.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITGA2B | ENST00000262407.6 | c.1913dupT | p.Cys639MetfsTer22 | frameshift_variant | Exon 19 of 30 | 1 | NM_000419.5 | ENSP00000262407.5 | ||
ITGA2B | ENST00000648408.1 | c.1343dupT | p.Cys449fs | frameshift_variant | Exon 15 of 25 | ENSP00000498119.1 | ||||
ITGA2B | ENST00000592462.5 | n.708dupT | non_coding_transcript_exon_variant | Exon 8 of 15 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000142 AC: 2AN: 1408592Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1AN XY: 695454
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
Glanzmann thrombasthenia Pathogenic:1
The ITGA2B frameshift variant NM_000419.5:c.1913dup (p.Cys639MetfsTer22) introduces a premature termination codon and the resulting mRNA product is predicted to undergo nonsense mediated decay, leading to loss of normal protein function. This variant has been observed in homozygosity in one individual (Patient LF, PMID: 12083483) and heterozygosity in two individuals (CabGT-2, PMID: 20020534 and Patient ER, PMID: 12083483), at least one of which was reported to have a phenotype specific for Glanzmann's thrombasthenia (GT). Furthermore, this variant is extremely rare in population databases. In summary, this variant meets criteria to be classified as pathogenic for GT. GT-specific criteria applied: PVS1, PP4_strong, PM2_supporting, PM3_supporting. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at