rs763707922

Variant names:

• chr21-44906941-T-C
• rs763707922
• NM_000211.5:c.302A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000211.5(ITGB2):​c.302A>G​(p.Gln101Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ITGB2 NM_000211.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58
• 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.922

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.302A>G	p.Gln101Arg	missense	Exon 4 of 16	NP_000202.3
	ITGB2	NM_001127491.3		c.302A>G	p.Gln101Arg	missense	Exon 4 of 16	NP_001120963.2
	ITGB2	NM_001303238.2		c.95A>G	p.Gln32Arg	missense	Exon 4 of 16	NP_001290167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.302A>G	p.Gln101Arg	missense	Exon 4 of 16	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.302A>G	p.Gln101Arg	missense	Exon 4 of 17	ENSP00000303242.6
	ITGB2	ENST00000397852.5	TSL:1	c.302A>G	p.Gln101Arg	missense	Exon 3 of 15	ENSP00000380950.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251446 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.000111 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Leukocyte adhesion deficiency 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.67	D
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.13	D
PhyloP100		2.6
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.46
Sift	Benign	0.13	T
Sift4G	Benign	0.14	T
Vest4		0.67
MutPred		0.93		Gain of MoRF binding (P = 0.0251)
MVP		0.91
MPC		0.45
ClinPred		0.20	T
GERP RS		2.1
gMVP		0.85
Mutation Taster		=83/17	polymorphism

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: rs763707922; hg19: chr21-46326856;