21-44886197-C-G

Position:

• chr21-44886197-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000211.5(ITGB2):​c.*171G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 675,362 control chromosomes in the GnomAD database, including 3,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (2668 hom., cov: 32)
  • Exomes 𝑓: 0.014 (1022 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.158

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 21-44886197-C-G is Benign according to our data. Variant chr21-44886197-C-G is described in ClinVar as [Benign]. Clinvar id is 340129.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.*171G>C		3_prime_UTR_variant	16/16	ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.*171G>C		3_prime_UTR_variant	16/16		NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15354 AN: 151980 Hom.: 2661 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.0866

GnomAD4 exome AF: 0.0140 AC: 7312 AN: 523264 Hom.: 1022 Cov.: 6 AF XY: 0.0113 AC XY: 3165 AN XY: 279274

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.0201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000319

Gnomad4 SAS exome AF: 0.00118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000933

Gnomad4 OTH exome AF: 0.0302

GnomAD4 genome AF: 0.101 AC: 15389 AN: 152098 Hom.: 2668 Cov.: 32 AF XY: 0.0970 AC XY: 7211 AN XY: 74366

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.0397

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.0857

Alfa AF: 0.00471 Hom.: 6

Bravo AF: 0.118

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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	-0.85
CADD	Benign	0.15
DANN	Benign	0.45

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: rs6570; hg19: chr21-46306112;