NM_000211.5:c.24G>T

Variant names:

• chr21-44910759-C-A
• rs11088969
• NM_000211.5:c.24G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000211.5(ITGB2):​c.24G>T​(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,613,330 control chromosomes in the GnomAD database, including 40,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3643 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37039 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5 O:2
• Conservation: PhyloP100: -0.915
• Publications: 10 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, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 21-44910759-C-A is Benign according to our data. Variant chr21-44910759-C-A is described in ClinVar as Benign. ClinVar VariationId is 100753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.915 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 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.24G>T	p.Leu8Leu	synonymous	Exon 2 of 16	NP_000202.3
	ITGB2	NM_001127491.3		c.24G>T	p.Leu8Leu	synonymous	Exon 2 of 16	NP_001120963.2
	ITGB2	NM_001303238.2		c.-227G>T		5_prime_UTR	Exon 2 of 16	NP_001290167.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.24G>T	p.Leu8Leu	synonymous	Exon 2 of 16	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.24G>T	p.Leu8Leu	synonymous	Exon 2 of 17	ENSP00000303242.6
	ITGB2	ENST00000397852.5	TSL:1	c.24G>T	p.Leu8Leu	synonymous	Exon 1 of 15	ENSP00000380950.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32261 AN: 152110 Hom.: 3638 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.230

GnomAD2 exomes AF: 0.211 AC: 52502 AN: 249404 AF XY: 0.223

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.0477

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.217 AC: 317345 AN: 1461102 Hom.: 37039 Cov.: 34 AF XY: 0.223 AC XY: 161738 AN XY: 726846

African (AFR) AF: 0.226 AC: 7555 AN: 33476

American (AMR) AF: 0.112 AC: 5006 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 7881 AN: 26098

East Asian (EAS) AF: 0.0524 AC: 2080 AN: 39662

South Asian (SAS) AF: 0.362 AC: 31161 AN: 86188

European-Finnish (FIN) AF: 0.189 AC: 10057 AN: 53304

Middle Eastern (MID) AF: 0.273 AC: 1576 AN: 5766

European-Non Finnish (NFE) AF: 0.215 AC: 238957 AN: 1111584

Other (OTH) AF: 0.217 AC: 13072 AN: 60366

GnomAD4 genome AF: 0.212 AC: 32289 AN: 152228 Hom.: 3643 Cov.: 33 AF XY: 0.213 AC XY: 15866 AN XY: 74430

African (AFR) AF: 0.224 AC: 9321 AN: 41528

American (AMR) AF: 0.153 AC: 2348 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3470

East Asian (EAS) AF: 0.0571 AC: 296 AN: 5186

South Asian (SAS) AF: 0.356 AC: 1720 AN: 4828

European-Finnish (FIN) AF: 0.194 AC: 2061 AN: 10614

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14660 AN: 67988

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.218 Hom.: 6219

Bravo AF: 0.204

Asia WGS AF: 0.192 AC: 670 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Leukocyte adhesion deficiency 1 (3)
-	-	2	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		-0.92
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs11088969; hg19: chr21-46330674; COSMIC: COSV56608127; COSMIC: COSV56608127;