Genetic Variant ITGB2:p.Glu630Gln (chr21-44888885-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000211.5(ITGB2):c.1888G>C(p.Glu630Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E630K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ITGB2
NM_000211.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

0 publications found

Variant links:

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

ITGB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40142432).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITGB2	NM_000211.5	MANE Select	c.1888G>C	p.Glu630Gln	missense	Exon 14 of 16	NP_000202.3
ITGB2	NM_001127491.3		c.1888G>C	p.Glu630Gln	missense	Exon 14 of 16	NP_001120963.2
ITGB2	NM_001303238.2		c.1681G>C	p.Glu561Gln	missense	Exon 14 of 16	NP_001290167.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITGB2	ENST00000652462.1	MANE Select	c.1888G>C	p.Glu630Gln	missense	Exon 14 of 16	ENSP00000498780.1
ITGB2	ENST00000302347.10	TSL:1	c.1960G>C	p.Glu654Gln	missense	Exon 15 of 17	ENSP00000303242.6
ITGB2	ENST00000397852.5	TSL:1	c.1888G>C	p.Glu630Gln	missense	Exon 13 of 15	ENSP00000380950.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453022

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111824

Other (OTH)

AF:

0.00

AC:

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

0.049

Eigen_PC

Benign

0.0019

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.40

MetaSVM

Uncertain

-0.20

PhyloP100

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.39

Sift

Benign

0.57

Sift4G

Benign

0.50

Vest4

0.16

MutPred

0.60

Loss of ubiquitination at K633 (P = 0.0374)

MVP

0.90

MPC

0.71

ClinPred

0.50

GERP RS

5.1

gMVP

0.51

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over