rs200335681
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000211.5(ITGB2):c.2078G>A(p.Arg693Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000074 in 1,607,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R693P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000211.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGB2 | NM_000211.5 | c.2078G>A | p.Arg693Gln | missense_variant, splice_region_variant | 14/16 | ENST00000652462.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGB2 | ENST00000652462.1 | c.2078G>A | p.Arg693Gln | missense_variant, splice_region_variant | 14/16 | NM_000211.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152254Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000813 AC: 20AN: 245928Hom.: 0 AF XY: 0.0000674 AC XY: 9AN XY: 133614
GnomAD4 exome AF: 0.0000728 AC: 106AN: 1455308Hom.: 0 Cov.: 33 AF XY: 0.0000773 AC XY: 56AN XY: 724276
GnomAD4 genome ? AF: 0.0000853 AC: 13AN: 152372Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74510
ClinVar
Submissions by phenotype
Leukocyte adhesion deficiency 1 Uncertain:2
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 19, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 693 of the ITGB2 protein (p.Arg693Gln). This variant is present in population databases (rs200335681, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ITGB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 340140). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at