rs17004715

Variant names:

• chr21-44903358-G-A
• rs17004715
• NM_000211.5:c.499+7C>T

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: 0.247
• Publications: 6 publications found

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]

ITGB2 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 340172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.499+7C>T		splice_region_variant, intron_variant	Intron 5 of 15	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.499+7C>T		splice_region_variant, intron_variant	Intron 5 of 15		NM_000211.5	ENSP00000498780.1

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

GnomAD2 exomes AF: 0.0213 AC: 5359 AN: 251192 AF XY: 0.0199

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 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

African (AFR) AF: 0.0872 AC: 2919 AN: 33478

American (AMR) AF: 0.0123 AC: 552 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0160 AC: 417 AN: 26134

East Asian (EAS) AF: 0.0525 AC: 2085 AN: 39698

South Asian (SAS) AF: 0.0143 AC: 1233 AN: 86254

European-Finnish (FIN) AF: 0.00794 AC: 424 AN: 53414

Middle Eastern (MID) AF: 0.0191 AC: 110 AN: 5768

European-Non Finnish (NFE) AF: 0.0131 AC: 14529 AN: 1111918

Other (OTH) AF: 0.0221 AC: 1334 AN: 60388

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

African (AFR) AF: 0.0827 AC: 3431 AN: 41506

American (AMR) AF: 0.0202 AC: 309 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3470

East Asian (EAS) AF: 0.0530 AC: 274 AN: 5166

South Asian (SAS) AF: 0.0178 AC: 86 AN: 4820

European-Finnish (FIN) AF: 0.00602 AC: 64 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0141 AC: 959 AN: 67990

Other (OTH) AF: 0.0298 AC: 63 AN: 2114

Alfa AF: 0.0220 Hom.: 64

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Leukocyte adhesion deficiency 1 Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.46
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17004715; hg19: chr21-46323273;