21-44886395-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_000211.5(ITGB2):c.2283C>T(p.Val761=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,614,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000037 ( 0 hom. )
Consequence
ITGB2
NM_000211.5 synonymous
NM_000211.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.910
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 21-44886395-G-A is Benign according to our data. Variant chr21-44886395-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 719017.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=0.91 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000788 (12/152342) while in subpopulation EAS AF= 0.00231 (12/5190). AF 95% confidence interval is 0.00133. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ITGB2 | NM_000211.5 | c.2283C>T | p.Val761= | synonymous_variant | 16/16 | ENST00000652462.1 | NP_000202.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ITGB2 | ENST00000652462.1 | c.2283C>T | p.Val761= | synonymous_variant | 16/16 | NM_000211.5 | ENSP00000498780 | P1 |
Frequencies
GnomAD3 genomes 0.0000788 AC: 12AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000171 AC: 43AN: 251452Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135904
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GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461834Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727230
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GnomAD4 genome 0.0000788 AC: 12AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74494
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Leukocyte adhesion deficiency 1 Uncertain:1Benign:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 17, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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