rs17004715

Positions:

• chr21-44903358-G-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.499+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,613,970 control chromosomes in the GnomAD database, including 500 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (151 hom., cov: 32)
  • Exomes 𝑓: 0.016 (349 hom.)
• Consequence: ITGB2 NM_000211.5 splice_region, intron
• Scores: Splicing: ADA: 0.0009559
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.247

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=-0.82).
• BP6: Variant 21-44903358-G-A is Benign according to our data. Variant chr21-44903358-G-A is described in ClinVar as [Benign]. Clinvar id is 340172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44903358-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.499+7C>T		splice_region_variant, intron_variant		ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.499+7C>T		splice_region_variant, intron_variant			NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5252 AN: 152080 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.00602

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0301

GnomAD3 exomes AF: 0.0213 AC: 5359 AN: 251192 Hom.: 133 AF XY: 0.0199 AC XY: 2701 AN XY: 135768

Gnomad AFR exome AF: 0.0842

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.0635

Gnomad SAS exome AF: 0.0145

Gnomad FIN exome AF: 0.00730

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.0192

GnomAD4 exome AF: 0.0161 AC: 23603 AN: 1461772 Hom.: 349 Cov.: 32 AF XY: 0.0159 AC XY: 11588 AN XY: 727202

Gnomad4 AFR exome AF: 0.0872

Gnomad4 AMR exome AF: 0.0123

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.0525

Gnomad4 SAS exome AF: 0.0143

Gnomad4 FIN exome AF: 0.00794

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.0221

GnomAD4 genome AF: 0.0345 AC: 5257 AN: 152198 Hom.: 151 Cov.: 32 AF XY: 0.0340 AC XY: 2527 AN XY: 74398

Gnomad4 AFR AF: 0.0827

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.0530

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.00602

Gnomad4 NFE AF: 0.0141

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0219 Hom.: 54

Bravo AF: 0.0380

Asia WGS AF: 0.0340 AC: 117 AN: 3478

EpiCase AF: 0.0149

EpiControl AF: 0.0145

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, 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 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

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00096
dbscSNV1_RF	Benign	0.030
SpliceAI score (max)		0.18		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: rs17004715; hg19: chr21-46323273;