rs61737081

chr21-44895052-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000211.5(ITGB2):c.1002C>T(p.Thr334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,094 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (31 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (18 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.61

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 21-44895052-G-A is Benign according to our data. Variant chr21-44895052-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 340160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44895052-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-5.61 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1539/152270) while in subpopulation AFR AF= 0.0342 (1422/41546). AF 95% confidence interval is 0.0327. There are 31 homozygotes in gnomad4. There are 747 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.1002C>T	p.Thr334=	synonymous_variant	9/16	ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.1002C>T	p.Thr334=	synonymous_variant	9/16		NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1531 AN: 152152 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00957

GnomAD3 exomes AF: 0.00279 AC: 702 AN: 251172 Hom.: 5 AF XY: 0.00218 AC XY: 296 AN XY: 135732

Gnomad AFR exome AF: 0.0344

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.000187

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00115 AC: 1680 AN: 1460824 Hom.: 18 Cov.: 30 AF XY: 0.000991 AC XY: 720 AN XY: 726774

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.00280

Gnomad4 ASJ exome AF: 0.00367

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.000245

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.00275

GnomAD4 genome AF: 0.0101 AC: 1539 AN: 152270 Hom.: 31 Cov.: 32 AF XY: 0.0100 AC XY: 747 AN XY: 74460

Gnomad4 AFR AF: 0.0342

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00576 Hom.: 7

Bravo AF: 0.0117

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

ITGB2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.050
Dann	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs61737081; hg19: chr21-46314967;