NM_000211.5:c.1101C>A

Variant names:

• chr21-44893527-G-T
• rs2230529
• NM_000211.5:c.1101C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000211.5(ITGB2):​c.1101C>A​(p.Val367Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,613,646 control chromosomes in the GnomAD database, including 48,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4337 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44550 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -0.249
• Publications: 15 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 21-44893527-G-T is Benign according to our data. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44893527-G-T is described in CliVar as Benign. Clinvar id is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.1101C>A	p.Val367Val	synonymous_variant	Exon 10 of 16	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.1101C>A	p.Val367Val	synonymous_variant	Exon 10 of 16		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35464 AN: 152008 Hom.: 4329 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.269

GnomAD2 exomes AF: 0.224 AC: 56404 AN: 251326 AF XY: 0.233

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.108

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.242 AC: 353317 AN: 1461520 Hom.: 44550 Cov.: 34 AF XY: 0.244 AC XY: 177186 AN XY: 727080

African (AFR) AF: 0.226 AC: 7549 AN: 33476

American (AMR) AF: 0.145 AC: 6485 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 7483 AN: 26124

East Asian (EAS) AF: 0.0967 AC: 3837 AN: 39696

South Asian (SAS) AF: 0.263 AC: 22706 AN: 86244

European-Finnish (FIN) AF: 0.173 AC: 9246 AN: 53344

Middle Eastern (MID) AF: 0.396 AC: 2283 AN: 5766

European-Non Finnish (NFE) AF: 0.251 AC: 279155 AN: 1111782

Other (OTH) AF: 0.241 AC: 14573 AN: 60376

GnomAD4 genome AF: 0.233 AC: 35484 AN: 152126 Hom.: 4337 Cov.: 32 AF XY: 0.230 AC XY: 17134 AN XY: 74386

African (AFR) AF: 0.225 AC: 9335 AN: 41508

American (AMR) AF: 0.216 AC: 3296 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3472

East Asian (EAS) AF: 0.104 AC: 536 AN: 5178

South Asian (SAS) AF: 0.250 AC: 1203 AN: 4808

European-Finnish (FIN) AF: 0.169 AC: 1786 AN: 10598

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17457 AN: 67952

Other (OTH) AF: 0.266 AC: 562 AN: 2110

Alfa AF: 0.252 Hom.: 5991

Bravo AF: 0.232

Asia WGS AF: 0.178 AC: 620 AN: 3478

EpiCase AF: 0.268

EpiControl AF: 0.278

ClinVar

Significance: Benign

Submissions summary: Benign:7 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:3 Other:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

not specified Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 39. Only high quality variants are reported. -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.5
DANN	Benign	0.80
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs2230529; hg19: chr21-46313442; COSMIC: COSV56610211; COSMIC: COSV56610211;