rs179363872

Variant names:

• chr21-44886836-C-G
• rs179363872
• NM_000211.5:c.2147G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PM5 PP3_Moderate

The NM_000211.5(ITGB2):​c.2147G>C​(p.Gly716Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G716R) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGB2 NM_000211.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 7.47
• Publications: 5 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr21-44886837-C-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 420118.Status of the report is criteria_provided_single_submitter, 1 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.2147G>C	p.Gly716Ala	missense_variant	Exon 15 of 16	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.2147G>C	p.Gly716Ala	missense_variant	Exon 15 of 16		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

UniProtKB/Swiss-Prot

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0	.;.;T;.;.;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.0	.;.;D;.;.;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.0	.;.;.;.;.;.
PhyloP100		7.5
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;D;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.013	D;D;D;D;D;D
Sift4G	Uncertain	0.024	D;D;D;D;D;D
Vest4		0.94
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.94
Mutation Taster		=3/97	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

Other links and lift over

dbSNP: rs179363872; hg19: chr21-46306751;