21-44885998-C-A

Variant names:

• chr21-44885998-C-A
• rs117989670
• NM_000211.5:c.*370G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000211.5(ITGB2):​c.*370G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 330,750 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (16 hom., cov: 33)
  • Exomes 𝑓: 0.011 (19 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.164
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 21-44885998-C-A is Benign according to our data. Variant chr21-44885998-C-A is described in ClinVar as Benign. ClinVar VariationId is 895891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.011 (1668/152076) while in subpopulation NFE AF = 0.0167 (1137/68010). AF 95% confidence interval is 0.0159. There are 16 homozygotes in GnomAd4. There are 787 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

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.*370G>T		3_prime_UTR	Exon 16 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.*370G>T		3_prime_UTR	Exon 16 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.*370G>T		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.*370G>T		3_prime_UTR	Exon 16 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.*370G>T		3_prime_UTR	Exon 17 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.*370G>T		3_prime_UTR	Exon 15 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1670 AN: 151958 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00322

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0111 AC: 1987 AN: 178674 Hom.: 19 Cov.: 0 AF XY: 0.0102 AC XY: 983 AN XY: 96304

African (AFR) AF: 0.00184 AC: 10 AN: 5428

American (AMR) AF: 0.00746 AC: 58 AN: 7770

Ashkenazi Jewish (ASJ) AF: 0.0160 AC: 72 AN: 4504

East Asian (EAS) AF: 0.00 AC: 0 AN: 8102

South Asian (SAS) AF: 0.00106 AC: 34 AN: 32026

European-Finnish (FIN) AF: 0.0103 AC: 83 AN: 8068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 682

European-Non Finnish (NFE) AF: 0.0157 AC: 1617 AN: 103106

Other (OTH) AF: 0.0126 AC: 113 AN: 8988

GnomAD4 genome AF: 0.0110 AC: 1668 AN: 152076 Hom.: 16 Cov.: 33 AF XY: 0.0106 AC XY: 787 AN XY: 74332

African (AFR) AF: 0.00321 AC: 133 AN: 41378

American (AMR) AF: 0.0112 AC: 171 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0167 AC: 1137 AN: 68010

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00572 Hom.: 2

Bravo AF: 0.0107

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.50
PhyloP100		-0.16
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: rs117989670; hg19: chr21-46305913;