21-44899502-A-G

Variant names:

• chr21-44899502-A-G
• rs2838729
• NM_000211.5:c.898-340T>C

Variant summary

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

The NM_000211.5(ITGB2):​c.898-340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,036 control chromosomes in the GnomAD database, including 22,705 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 0.53 (22705 hom., cov: 33)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.22
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.898-340T>C		intron_variant	Intron 7 of 15	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.898-340T>C		intron_variant	Intron 7 of 15		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80192 AN: 151918 Hom.: 22653 Cov.: 33

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.528 AC: 80316 AN: 152036 Hom.: 22705 Cov.: 33 AF XY: 0.530 AC XY: 39392 AN XY: 74310

African (AFR) AF: 0.737 AC: 30577 AN: 41476

American (AMR) AF: 0.461 AC: 7035 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1432 AN: 3468

East Asian (EAS) AF: 0.676 AC: 3482 AN: 5152

South Asian (SAS) AF: 0.451 AC: 2174 AN: 4824

European-Finnish (FIN) AF: 0.531 AC: 5623 AN: 10584

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28577 AN: 67942

Other (OTH) AF: 0.490 AC: 1033 AN: 2110

Alfa AF: 0.444 Hom.: 17909

Bravo AF: 0.535

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-6.2
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: rs2838729; hg19: chr21-46319417;