21-44887580-T-C

Variant names:

• chr21-44887580-T-C
• rs180318
• NM_000211.5:c.2081-678A>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.2081-678A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,652 control chromosomes in the GnomAD database, including 38,096 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 0.70 (38096 hom., cov: 31)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 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.2081-678A>G		intron	N/A	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.2081-678A>G		intron	N/A	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.1874-678A>G		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.2081-678A>G		intron	N/A	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.2153-678A>G		intron	N/A	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.2081-678A>G		intron	N/A	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105466 AN: 151534 Hom.: 38031 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.696 AC: 105597 AN: 151652 Hom.: 38096 Cov.: 31 AF XY: 0.696 AC XY: 51602 AN XY: 74110

African (AFR) AF: 0.892 AC: 36887 AN: 41370

American (AMR) AF: 0.626 AC: 9549 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2124 AN: 3466

East Asian (EAS) AF: 0.808 AC: 4153 AN: 5138

South Asian (SAS) AF: 0.689 AC: 3309 AN: 4800

European-Finnish (FIN) AF: 0.619 AC: 6535 AN: 10552

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.604 AC: 40942 AN: 67774

Other (OTH) AF: 0.706 AC: 1488 AN: 2108

Alfa AF: 0.644 Hom.: 7382

Bravo AF: 0.707

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
DANN	Benign	0.37
PhyloP100		-1.7
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: rs180318; hg19: chr21-46307495; COSMIC: COSV56612321;