chr17-44380626-G-C
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000419.5(ITGA2B):c.1413C>G(p.Tyr471Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★). Synonymous variant affecting the same amino acid position (i.e. Y471Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000419.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGA2B | NM_000419.5 | c.1413C>G | p.Tyr471Ter | stop_gained | 14/30 | ENST00000262407.6 | |
ITGA2B | XM_011524749.2 | c.1566C>G | p.Tyr522Ter | stop_gained | 14/29 | ||
ITGA2B | XM_011524750.2 | c.1566C>G | p.Tyr522Ter | stop_gained | 14/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA2B | ENST00000262407.6 | c.1413C>G | p.Tyr471Ter | stop_gained | 14/30 | 1 | NM_000419.5 | P1 | |
ITGA2B | ENST00000648408.1 | c.846C>G | p.Tyr282Ter | stop_gained | 10/25 | ||||
ITGA2B | ENST00000592226.5 | n.886C>G | non_coding_transcript_exon_variant | 7/10 | 5 | ||||
ITGA2B | ENST00000592462.5 | n.208C>G | non_coding_transcript_exon_variant | 3/15 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251476Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461892Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727248
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
ClinVar
Submissions by phenotype
Glanzmann thrombasthenia Pathogenic:1
Pathogenic, reviewed by expert panel | curation | ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen | Sep 06, 2020 | The ITGA2B nonsense variant NM_000419.4:c.1413C>G (p.Tyr471Ter) 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 a proband with a phenotype specific for Glanzmann's thrombasthenia (GT) who also harbors a second ITGA2B variant (c.1882C>T, p.Arg628Ter) previously classified by the VCEP as pathogenic. Furthermore, this variant has been reported in low frequencies in population databases (<1/10,000 alleles in gnomAD). In summary, this variant meets criteria to be classified as pathogenic for GT. GT-specific criteria applied: PVS1, PM2_Supporting, PM3_supporting, and PP4_strong. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at