rs2230531
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000211.5(ITGB2):c.1888G>A(p.Glu630Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00633 in 1,605,294 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0051 ( 8 hom., cov: 34)
Exomes 𝑓: 0.0065 ( 50 hom. )
Consequence
ITGB2
NM_000211.5 missense
NM_000211.5 missense
Scores
1
9
7
Clinical Significance
Conservation
PhyloP100: 1.85
Genes affected
ITGB2 (HGNC:6155): (integrin subunit beta 2) This gene encodes an integrin beta chain, which combines with multiple different alpha chains to form different integrin heterodimers. Integrins are integral cell-surface proteins that participate in cell adhesion as well as cell-surface mediated signalling. The encoded protein plays an important role in immune response and defects in this gene cause leukocyte adhesion deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.018218666).
BP6
Variant 21-44888885-C-T is Benign according to our data. Variant chr21-44888885-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44888885-C-T is described in Lovd as [Likely_benign]. Variant chr21-44888885-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00508 (773/152280) while in subpopulation NFE AF= 0.00644 (438/68014). AF 95% confidence interval is 0.00594. There are 8 homozygotes in gnomad4. There are 431 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGB2 | NM_000211.5 | c.1888G>A | p.Glu630Lys | missense_variant | 14/16 | ENST00000652462.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGB2 | ENST00000652462.1 | c.1888G>A | p.Glu630Lys | missense_variant | 14/16 | NM_000211.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00508 AC: 773AN: 152160Hom.: 8 Cov.: 34
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GnomAD3 exomes AF: 0.00496 AC: 1200AN: 241732Hom.: 13 AF XY: 0.00491 AC XY: 648AN XY: 132080
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GnomAD4 exome AF: 0.00646 AC: 9381AN: 1453014Hom.: 50 Cov.: 33 AF XY: 0.00635 AC XY: 4589AN XY: 723150
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GnomAD4 genome AF: 0.00508 AC: 773AN: 152280Hom.: 8 Cov.: 34 AF XY: 0.00579 AC XY: 431AN XY: 74456
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Leukocyte adhesion deficiency 1 Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 22, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Jul 15, 2022 | This variant has been reported in the literature in at least 10 individuals with chronic lymphocytic leukemia (CLL) (Goldin 2016 PMID:27629550, Blackburn 2017 PMID:28490671); however at least 1 study did not identify an enrichment of the variant in cases vs. controls. This variant was also identified in 3 individuals with congenital heart defects (Russell 2019 PMID:31453292). This variant is present in the Genome Aggregation Database (Highest reported MAF 2.1% (226/10616) including 8 homozygotes (https://gnomad.broadinstitute.org/variant/21-44888885-C-T?dataset=gnomad_r3). This variant is present in ClinVar, with multiple labs classifying this variant as Benign or Likely Benign (Variation ID:445547). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. - |
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | ITGB2: BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 16, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;T;.;.;T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
N;N;D;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Vest4
MVP
MPC
1.1
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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