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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000211.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.499+7C>T		splice_region intron	N/A	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.499+7C>T		splice_region intron	N/A	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.292+7C>T		splice_region intron	N/A	NP_001290167.1	B4E0R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.499+7C>T		splice_region intron	N/A	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.499+7C>T		splice_region intron	N/A	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.499+7C>T		splice_region intron	N/A	ENSP00000380950.1	P05107

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Leukocyte adhesion deficiency 1 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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;