Genetic Variant NM_000211.5:c.281G>C (chr21-44906962-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000211.5(ITGB2):c.281G>C(p.Gly94Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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. G94D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ITGB2
NM_000211.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.03

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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ITGB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.086596906).

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	UniProt
ITGB2	NM_000211.5	MANE Select	c.281G>C	p.Gly94Ala	missense	Exon 4 of 16	NP_000202.3	P05107
ITGB2	NM_001127491.3		c.281G>C	p.Gly94Ala	missense	Exon 4 of 16	NP_001120963.2	P05107
ITGB2	NM_001303238.2		c.74G>C	p.Gly25Ala	missense	Exon 4 of 16	NP_001290167.1	B4E0R1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGB2	ENST00000652462.1	MANE Select	c.281G>C	p.Gly94Ala	missense	Exon 4 of 16	ENSP00000498780.1	A0A494C0X7
ITGB2	ENST00000302347.10	TSL:1	c.281G>C	p.Gly94Ala	missense	Exon 4 of 17	ENSP00000303242.6	A0AAA9WZN5
ITGB2	ENST00000397852.5	TSL:1	c.281G>C	p.Gly94Ala	missense	Exon 3 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251458

AF XY:

0.00

show subpopulations

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.14

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.31

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.54

M_CAP

Benign

0.063

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.61

PhyloP100

-3.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.99

REVEL

Benign

0.21

Sift

Benign

0.30

Sift4G

Benign

0.40

Vest4

0.19

MutPred

0.25

Loss of sheet (P = 0.0817)

MVP

0.73

MPC

0.35

ClinPred

0.057

GERP RS

-4.2

gMVP

0.28

Mutation Taster

=86/14

polymorphism

(source)

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

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