21-44900398-C-T

Position:

chr21-44900398-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000211.5(ITGB2):c.819G>A(p.Gly273Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,910 control chromosomes in the GnomAD database, including 46,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3987 hom., cov: 33)

Exomes 𝑓: 0.24 ( 42057 hom. )

Consequence

ITGB2
NM_000211.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:2

Conservation

PhyloP100: 0.509

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 links:

ITGB2 (HGNC:):

ITGB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 21-44900398-C-T is Benign according to our data. Variant chr21-44900398-C-T is described in ClinVar as [Benign]. Clinvar id is 100761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44900398-C-T is described in Lovd as [Benign]. Variant chr21-44900398-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.509 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_000211.5 linkuse as main transcript	c.819G>A	p.Gly273Gly	synonymous_variant	7/16	ENST00000652462.1	NP_000202.3	P05107A0A494C0X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1 linkuse as main transcript	c.819G>A	p.Gly273Gly	synonymous_variant	7/16		NM_000211.5	ENSP00000498780.1		A0A494C0X7

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33913

AN:

152064

Hom.:

3985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.226

GnomAD3 exomes

AF:

0.247

AC:

61952

AN:

251256

Hom.:

8314

AF XY:

0.247

AC XY:

33546

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.368

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.140

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.236

AC:

345309

AN:

1461728

Hom.:

42057

Cov.:

AF XY:

0.238

AC XY:

173225

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.358

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.223

AC:

33917

AN:

152182

Hom.:

3987

Cov.:

AF XY:

0.223

AC XY:

16562

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.309

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.240

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.236

Hom.:

3610

Bravo

AF:

0.226

Asia WGS

AF:

0.244

AC:

848

AN:

3478

EpiCase

AF:

0.234

EpiControl

AF:

0.246

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 1

Benign:3Other:1

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided, no classification provided	literature only	Genomic Research Center, Shahid Beheshti University of Medical Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.2

DANN

Benign

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over