21-44886018-AT-A

Position:

• chr21-44886018-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000211.5(ITGB2):​c.*349del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 368,236 control chromosomes in the GnomAD database, including 131 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (114 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (17 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.657

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 -10 ACMG points.

• BP6: Variant 21-44886018-AT-A is Benign according to our data. Variant chr21-44886018-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 340127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.*349del		3_prime_UTR_variant	16/16	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.*349del		3_prime_UTR_variant	16/16		NM_000211.5	ENSP00000498780	P1

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3140 AN: 152100 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.00423 AC: 913 AN: 216018 Hom.: 17 Cov.: 0 AF XY: 0.00389 AC XY: 449 AN XY: 115494

Gnomad4 AFR exome AF: 0.0628

Gnomad4 AMR exome AF: 0.00568

Gnomad4 ASJ exome AF: 0.000168

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000546

Gnomad4 FIN exome AF: 0.000885

Gnomad4 NFE exome AF: 0.00260

Gnomad4 OTH exome AF: 0.00671

GnomAD4 genome AF: 0.0207 AC: 3147 AN: 152218 Hom.: 114 Cov.: 32 AF XY: 0.0202 AC XY: 1500 AN XY: 74434

Gnomad4 AFR AF: 0.0670

Gnomad4 AMR AF: 0.00870

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00278

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0141 Hom.: 4

Bravo AF: 0.0224

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leukocyte adhesion deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs145404701; hg19: chr21-46305933;