rs684

chr21-44886246-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000211.5(ITGB2):c.*122G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,002,834 control chromosomes in the GnomAD database, including 22,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3090 hom., cov: 31)
  • Exomes 𝑓: 0.21 (19091 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.420

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 21-44886246-C-T is Benign according to our data. Variant chr21-44886246-C-T is described in ClinVar as [Benign]. Clinvar id is 340134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.*122G>A		3_prime_UTR_variant	16/16	ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.*122G>A		3_prime_UTR_variant	16/16		NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29765 AN: 151796 Hom.: 3085 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.206 AC: 175103 AN: 850920 Hom.: 19091 Cov.: 11 AF XY: 0.208 AC XY: 92222 AN XY: 444294

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.0923

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.196 AC: 29778 AN: 151914 Hom.: 3090 Cov.: 31 AF XY: 0.192 AC XY: 14260 AN XY: 74230

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.0840

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.223

Alfa AF: 0.223 Hom.: 2268

Bravo AF: 0.195

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Leukocyte adhesion deficiency 1 Benign: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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.5
Dann	Benign	0.63

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

Other links and lift over

dbSNP: rs684; hg19: chr21-46306161; COSMIC: COSV56609304; COSMIC: COSV56609304;