chr5-53042153-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong
The NM_002203.4(ITGA2):c.227G>A(p.Arg76Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,613,362 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0031 ( 15 hom. )
Consequence
ITGA2
NM_002203.4 missense
NM_002203.4 missense
Scores
5
5
6
Clinical Significance
Conservation
PhyloP100: 8.04
Genes affected
ITGA2 (HGNC:6137): (integrin subunit alpha 2) This gene encodes the alpha subunit of a transmembrane receptor for collagens and related proteins. The encoded protein forms a heterodimer with a beta subunit and mediates the adhesion of platelets and other cell types to the extracellular matrix. Loss of the encoded protein is associated with bleeding disorder platelet-type 9. Antibodies against this protein are found in several immune disorders, including neonatal alloimmune thrombocytopenia. This gene is located adjacent to a related alpha subunit gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0881674).
BP6
?
Variant 5-53042153-G-A is Benign according to our data. Variant chr5-53042153-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 353733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-53042153-G-A is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGA2 | NM_002203.4 | c.227G>A | p.Arg76Gln | missense_variant | 3/30 | ENST00000296585.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA2 | ENST00000296585.10 | c.227G>A | p.Arg76Gln | missense_variant | 3/30 | 1 | NM_002203.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00219 AC: 333AN: 152142Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00244 AC: 614AN: 251290Hom.: 1 AF XY: 0.00235 AC XY: 319AN XY: 135816
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GnomAD4 exome AF: 0.00305 AC: 4457AN: 1461102Hom.: 15 Cov.: 31 AF XY: 0.00298 AC XY: 2164AN XY: 726876
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
ITGA2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 11, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Platelet-type bleeding disorder 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at