21-44886223-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000211.5(ITGB2):​c.*145C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 803,680 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

ITGB2
NM_000211.5 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.227
Variant links:
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 Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGB2NM_000211.5 linkuse as main transcriptc.*145C>T 3_prime_UTR_variant 16/16 ENST00000652462.1 NP_000202.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGB2ENST00000652462.1 linkuse as main transcriptc.*145C>T 3_prime_UTR_variant 16/16 NM_000211.5 ENSP00000498780 P1

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
31
AN:
151980
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.000955
GnomAD4 exome
AF:
0.000238
AC:
155
AN:
651582
Hom.:
1
Cov.:
9
AF XY:
0.000274
AC XY:
95
AN XY:
346382
show subpopulations
Gnomad4 AFR exome
AF:
0.000389
Gnomad4 AMR exome
AF:
0.000220
Gnomad4 ASJ exome
AF:
0.00170
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000304
Gnomad4 FIN exome
AF:
0.0000447
Gnomad4 NFE exome
AF:
0.000224
Gnomad4 OTH exome
AF:
0.000240
GnomAD4 genome
AF:
0.000224
AC:
34
AN:
152098
Hom.:
1
Cov.:
32
AF XY:
0.000269
AC XY:
20
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000167
Hom.:
203

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
4.7
DANN
Benign
0.46
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1160263; hg19: chr21-46306138; API