rs2230529

Variant names:

• chr21-44893527-G-T
• rs2230529
• NM_000211.5:c.1101C>A
• ITGB2 p.Val367Val

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.1101C>A​(p.Val367Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,613,646 control chromosomes in the GnomAD database, including 48,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4337 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44550 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9 O:1
• Conservation: PhyloP100: -0.249
• Publications: 15 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 21-44893527-G-T is Benign according to our data. Variant chr21-44893527-G-T is described in ClinVar as Benign. ClinVar VariationId is 100746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 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.1101C>A	p.Val367Val	synonymous	Exon 10 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.1101C>A	p.Val367Val	synonymous	Exon 10 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.894C>A	p.Val298Val	synonymous	Exon 10 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.1101C>A	p.Val367Val	synonymous	Exon 10 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.1173C>A	p.Val391Val	synonymous	Exon 11 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.1101C>A	p.Val367Val	synonymous	Exon 9 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35464 AN: 152008 Hom.: 4329 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.269

GnomAD2 exomes AF: 0.224 AC: 56404 AN: 251326 AF XY: 0.233

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.108

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.242 AC: 353317 AN: 1461520 Hom.: 44550 Cov.: 34 AF XY: 0.244 AC XY: 177186 AN XY: 727080

African (AFR) AF: 0.226 AC: 7549 AN: 33476

American (AMR) AF: 0.145 AC: 6485 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 7483 AN: 26124

East Asian (EAS) AF: 0.0967 AC: 3837 AN: 39696

South Asian (SAS) AF: 0.263 AC: 22706 AN: 86244

European-Finnish (FIN) AF: 0.173 AC: 9246 AN: 53344

Middle Eastern (MID) AF: 0.396 AC: 2283 AN: 5766

European-Non Finnish (NFE) AF: 0.251 AC: 279155 AN: 1111782

Other (OTH) AF: 0.241 AC: 14573 AN: 60376

GnomAD4 genome AF: 0.233 AC: 35484 AN: 152126 Hom.: 4337 Cov.: 32 AF XY: 0.230 AC XY: 17134 AN XY: 74386

African (AFR) AF: 0.225 AC: 9335 AN: 41508

American (AMR) AF: 0.216 AC: 3296 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3472

East Asian (EAS) AF: 0.104 AC: 536 AN: 5178

South Asian (SAS) AF: 0.250 AC: 1203 AN: 4808

European-Finnish (FIN) AF: 0.169 AC: 1786 AN: 10598

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17457 AN: 67952

Other (OTH) AF: 0.266 AC: 562 AN: 2110

Alfa AF: 0.252 Hom.: 5991

Bravo AF: 0.232

Asia WGS AF: 0.178 AC: 620 AN: 3478

EpiCase AF: 0.268

EpiControl AF: 0.278

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Leukocyte adhesion deficiency 1 (4)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.5
DANN	Benign	0.80
PhyloP100		-0.25
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2230529;

hg19: chr21-46313442;

COSMIC: COSV56610211;

COSMIC: COSV56610211;