rs5030668

chr21-44906900-C-Tchr21-44906900-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000211.5(ITGB2):c.328+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,630 control chromosomes in the GnomAD database, including 19,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1677 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17682 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.84

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-44906900-C-T is Benign according to our data. Variant chr21-44906900-C-T is described in ClinVar as [Benign]. Clinvar id is 340174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44906900-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.328+15G>A		intron_variant		ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.328+15G>A		intron_variant			NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20040 AN: 152132 Hom.: 1678 Cov.: 32

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.157 AC: 39354 AN: 250890 Hom.: 3592 AF XY: 0.152 AC XY: 20628 AN XY: 135686

Gnomad AFR exome AF: 0.0442

Gnomad AMR exome AF: 0.269

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.132

Gnomad SAS exome AF: 0.0909

Gnomad FIN exome AF: 0.176

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.151 AC: 221135 AN: 1461380 Hom.: 17682 Cov.: 33 AF XY: 0.150 AC XY: 108699 AN XY: 727016

Gnomad4 AFR exome AF: 0.0413

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.0955

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.132 AC: 20041 AN: 152250 Hom.: 1677 Cov.: 32 AF XY: 0.134 AC XY: 9987 AN XY: 74450

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.0844

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.114

Alfa AF: 0.138 Hom.: 370

Bravo AF: 0.131

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -

Leukocyte adhesion deficiency 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.0060
Dann	Benign	0.36

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

Other links and lift over

dbSNP: rs5030668; hg19: chr21-46326815; COSMIC: COSV56607815; COSMIC: COSV56607815;