rs2838734

Variant names:

• chr21-44909825-T-C
• rs2838734
• NM_000211.5:c.147+459A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000211.5(ITGB2):​c.147+459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,136 control chromosomes in the GnomAD database, including 11,942 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (11942 hom., cov: 33)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 15 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

LOC107987303 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.515 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.147+459A>G		intron	N/A	NP_000202.3
	ITGB2	NM_001127491.3		c.147+459A>G		intron	N/A	NP_001120963.2
	ITGB2	NM_001303238.2		c.-61+459A>G		intron	N/A	NP_001290167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.147+459A>G		intron	N/A	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.147+459A>G		intron	N/A	ENSP00000303242.6
	ITGB2	ENST00000397852.5	TSL:1	c.147+459A>G		intron	N/A	ENSP00000380950.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58653 AN: 152018 Hom.: 11923 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.412

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.386 AC: 58685 AN: 152136 Hom.: 11942 Cov.: 33 AF XY: 0.383 AC XY: 28499 AN XY: 74364

African (AFR) AF: 0.258 AC: 10722 AN: 41506

American (AMR) AF: 0.525 AC: 8023 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1548 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2357 AN: 5164

South Asian (SAS) AF: 0.349 AC: 1684 AN: 4820

European-Finnish (FIN) AF: 0.311 AC: 3297 AN: 10586

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29569 AN: 67980

Other (OTH) AF: 0.408 AC: 862 AN: 2112

Alfa AF: 0.433 Hom.: 24733

Bravo AF: 0.396

Asia WGS AF: 0.425 AC: 1478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.55
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2838734; hg19: chr21-46329740;