NM_000211.5:c.1635C>T

Variant names:

• chr21-44890000-G-A
• rs61747606
• NM_000211.5:c.1635C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000211.5(ITGB2):​c.1635C>T​(p.Asn545Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,613,360 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (17 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.64
• Publications: 8 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=-0.88).
• BP6: Variant 21-44890000-G-A is Benign according to our data. Variant chr21-44890000-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 530688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00144 (220/152322) while in subpopulation SAS AF = 0.00601 (29/4828). AF 95% confidence interval is 0.0043. There are 0 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 17 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.1635C>T	p.Asn545Asn	synonymous	Exon 12 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.1635C>T	p.Asn545Asn	synonymous	Exon 12 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.1428C>T	p.Asn476Asn	synonymous	Exon 12 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.1635C>T	p.Asn545Asn	synonymous	Exon 12 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.1707C>T	p.Asn569Asn	synonymous	Exon 13 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.1635C>T	p.Asn545Asn	synonymous	Exon 11 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 220 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00216

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00224 AC: 562 AN: 250764 AF XY: 0.00237

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00291

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00212 AC: 3094 AN: 1461038 Hom.: 17 Cov.: 33 AF XY: 0.00223 AC XY: 1623 AN XY: 726834

African (AFR) AF: 0.000627 AC: 21 AN: 33480

American (AMR) AF: 0.000648 AC: 29 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000918 AC: 24 AN: 26134

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.00580 AC: 500 AN: 86256

European-Finnish (FIN) AF: 0.00110 AC: 58 AN: 52594

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00208 AC: 2314 AN: 1112000

Other (OTH) AF: 0.00232 AC: 140 AN: 60386

GnomAD4 genome AF: 0.00144 AC: 220 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.00154 AC XY: 115 AN XY: 74474

African (AFR) AF: 0.000361 AC: 15 AN: 41572

American (AMR) AF: 0.000784 AC: 12 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4828

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00216 AC: 147 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00210 Hom.: 0

Bravo AF: 0.00142

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Leukocyte adhesion deficiency 1 (2)
-	-	2	not provided (2)
-	-	1	ITGB2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.15
DANN	Benign	0.55
PhyloP100		-4.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs61747606; hg19: chr21-46309915; COSMIC: COSV56607348; COSMIC: COSV56607348;