rs138659490
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_000211.5(ITGB2):c.1358G>A(p.Ser453Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00065 in 1,611,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000211.5 missense
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.1358G>A | p.Ser453Asn | missense_variant | 11/16 | ENST00000652462.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGB2 | ENST00000652462.1 | c.1358G>A | p.Ser453Asn | missense_variant | 11/16 | NM_000211.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000532 AC: 81AN: 152254Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000533 AC: 133AN: 249544Hom.: 0 AF XY: 0.000577 AC XY: 78AN XY: 135180
GnomAD4 exome AF: 0.000663 AC: 967AN: 1459520Hom.: 0 Cov.: 30 AF XY: 0.000628 AC XY: 456AN XY: 726148
GnomAD4 genome ? AF: 0.000532 AC: 81AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37AN XY: 74380
ClinVar
Submissions by phenotype
Leukocyte adhesion deficiency 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 18, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 453 of the ITGB2 protein (p.Ser453Asn). This variant is present in population databases (rs138659490, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with leukocyte adhesion deficiency (PMID: 22134107). ClinVar contains an entry for this variant (Variation ID: 530681). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect ITGB2 function (PMID: 25514840). 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