21-44891898-A-G

Variant names:

• chr21-44891898-A-G
• rs235326
• NM_000211.5:c.1323T>C

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.1323T>C​(p.Val441Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,612,870 control chromosomes in the GnomAD database, including 375,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V441V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.74 (42687 hom., cov: 34)
  • Exomes 𝑓: 0.67 (332767 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9 O:1
• Conservation: PhyloP100: -2.01
• Publications: 41 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 21-44891898-A-G is Benign according to our data. Variant chr21-44891898-A-G is described in ClinVar as Benign. ClinVar VariationId is 340155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 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.1323T>C	p.Val441Val	synonymous	Exon 11 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.1323T>C	p.Val441Val	synonymous	Exon 11 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.1116T>C	p.Val372Val	synonymous	Exon 11 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.1323T>C	p.Val441Val	synonymous	Exon 11 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.1395T>C	p.Val465Val	synonymous	Exon 12 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.1323T>C	p.Val441Val	synonymous	Exon 10 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112334 AN: 152094 Hom.: 42620 Cov.: 34

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.739

GnomAD2 exomes AF: 0.681 AC: 170459 AN: 250414 AF XY: 0.678

Gnomad AFR exome AF: 0.926

Gnomad AMR exome AF: 0.582

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.797

Gnomad FIN exome AF: 0.672

Gnomad NFE exome AF: 0.670

Gnomad OTH exome AF: 0.672

GnomAD4 exome AF: 0.673 AC: 982670 AN: 1460658 Hom.: 332767 Cov.: 62 AF XY: 0.671 AC XY: 487857 AN XY: 726650

African (AFR) AF: 0.931 AC: 31184 AN: 33480

American (AMR) AF: 0.592 AC: 26461 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 17370 AN: 26132

East Asian (EAS) AF: 0.766 AC: 30423 AN: 39700

South Asian (SAS) AF: 0.646 AC: 55756 AN: 86256

European-Finnish (FIN) AF: 0.667 AC: 34891 AN: 52316

Middle Eastern (MID) AF: 0.772 AC: 4449 AN: 5766

European-Non Finnish (NFE) AF: 0.666 AC: 740468 AN: 1111920

Other (OTH) AF: 0.690 AC: 41668 AN: 60380

GnomAD4 genome AF: 0.739 AC: 112467 AN: 152212 Hom.: 42687 Cov.: 34 AF XY: 0.736 AC XY: 54785 AN XY: 74414

African (AFR) AF: 0.923 AC: 38350 AN: 41558

American (AMR) AF: 0.661 AC: 10120 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2299 AN: 3468

East Asian (EAS) AF: 0.778 AC: 4025 AN: 5174

South Asian (SAS) AF: 0.653 AC: 3152 AN: 4824

European-Finnish (FIN) AF: 0.671 AC: 7118 AN: 10602

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45138 AN: 67968

Other (OTH) AF: 0.743 AC: 1570 AN: 2112

Alfa AF: 0.674 Hom.: 23759

Bravo AF: 0.747

Asia WGS AF: 0.738 AC: 2567 AN: 3478

EpiCase AF: 0.677

EpiControl AF: 0.683

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 (3)
-	-	2	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs235326; hg19: chr21-46311813; COSMIC: COSV56608840; COSMIC: COSV56608840;