ITGB2 p.Gly169Arg

Variant names:

• chr21-44901728-C-G
• NM_000211.5:c.505G>C
• ITGB2 p.Gly169Arg

Your query was ambiguous. Multiple possible variants found:

• chr21-44901728-C-G
• chr21-44901728-C-T
• chr21-44901726-CCC-ACG
• chr21-44901726-CCC-GCG
• chr21-44901726-CCC-TCG
• chr21-44901726-CCC-TCT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PS1 PM1 PM2 PP3_Strong

The NM_000211.5(ITGB2):​c.505G>C​(p.Gly169Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ITGB2 NM_000211.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PS1: Transcript NM_000211.5 (ITGB2) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PM1: In a domain VWFA (size 239) in uniprot entity ITB2_HUMAN there are 14 pathogenic changes around while only 3 benign (82%) in NM_000211.5
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.993

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.505G>C	p.Gly169Arg	missense	Exon 6 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.505G>C	p.Gly169Arg	missense	Exon 6 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.298G>C	p.Gly100Arg	missense	Exon 6 of 16	NP_001290167.1	B4E0R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.505G>C	p.Gly169Arg	missense	Exon 6 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.505G>C	p.Gly169Arg	missense	Exon 6 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.505G>C	p.Gly169Arg	missense	Exon 5 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.51	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	1.1	D
PhyloP100		5.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-7.6	D
REVEL	Pathogenic	0.95
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.068	T
gMVP		0.97
Mutation Taster		=0/100	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-46321643;