21-44886018-AT-A

Variant names:

• chr21-44886018-AT-A
• rs145404701
• NM_000211.5:c.*349delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000211.5(ITGB2):​c.*349delA 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
• Publications: 0 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000211.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.*349delA		3_prime_UTR	Exon 16 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.*349delA		3_prime_UTR	Exon 16 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.*349delA		3_prime_UTR	Exon 16 of 16	NP_001290167.1	B4E0R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.*349delA		3_prime_UTR	Exon 16 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.*349delA		3_prime_UTR	Exon 17 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.*349delA		3_prime_UTR	Exon 15 of 15	ENSP00000380950.1	P05107

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

African (AFR) AF: 0.0628 AC: 414 AN: 6588

American (AMR) AF: 0.00568 AC: 54 AN: 9514

Ashkenazi Jewish (ASJ) AF: 0.000168 AC: 1 AN: 5968

East Asian (EAS) AF: 0.00 AC: 0 AN: 10928

South Asian (SAS) AF: 0.000546 AC: 19 AN: 34808

European-Finnish (FIN) AF: 0.000885 AC: 9 AN: 10168

Middle Eastern (MID) AF: 0.0138 AC: 12 AN: 870

European-Non Finnish (NFE) AF: 0.00260 AC: 327 AN: 125702

Other (OTH) AF: 0.00671 AC: 77 AN: 11472

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

African (AFR) AF: 0.0670 AC: 2781 AN: 41494

American (AMR) AF: 0.00870 AC: 133 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00278 AC: 189 AN: 68006

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0141 Hom.: 4

Bravo AF: 0.0224

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leukocyte adhesion deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism

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: rs145404701; hg19: chr21-46305933;