NM_000211.5:c.328+15G>A

Variant names:

• chr21-44906900-C-T
• rs5030668
• NM_000211.5:c.328+15G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000211.5(ITGB2):​c.328+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,630 control chromosomes in the GnomAD database, including 19,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1677 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17682 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.84
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-44906900-C-T is Benign according to our data. Variant chr21-44906900-C-T is described in ClinVar as Benign. ClinVar VariationId is 340174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.213 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.328+15G>A		intron	N/A	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.328+15G>A		intron	N/A	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.121+15G>A		intron	N/A	NP_001290167.1	B4E0R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.328+15G>A		intron	N/A	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.328+15G>A		intron	N/A	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.328+15G>A		intron	N/A	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20040 AN: 152132 Hom.: 1678 Cov.: 32

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.157 AC: 39354 AN: 250890 AF XY: 0.152

Gnomad AFR exome AF: 0.0442

Gnomad AMR exome AF: 0.269

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.176

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.151 AC: 221135 AN: 1461380 Hom.: 17682 Cov.: 33 AF XY: 0.150 AC XY: 108699 AN XY: 727016

African (AFR) AF: 0.0413 AC: 1381 AN: 33478

American (AMR) AF: 0.260 AC: 11642 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 4424 AN: 26134

East Asian (EAS) AF: 0.110 AC: 4356 AN: 39696

South Asian (SAS) AF: 0.0955 AC: 8233 AN: 86242

European-Finnish (FIN) AF: 0.177 AC: 9429 AN: 53394

Middle Eastern (MID) AF: 0.0989 AC: 570 AN: 5764

European-Non Finnish (NFE) AF: 0.155 AC: 171911 AN: 1111600

Other (OTH) AF: 0.152 AC: 9189 AN: 60372

GnomAD4 genome AF: 0.132 AC: 20041 AN: 152250 Hom.: 1677 Cov.: 32 AF XY: 0.134 AC XY: 9987 AN XY: 74450

African (AFR) AF: 0.0457 AC: 1901 AN: 41568

American (AMR) AF: 0.219 AC: 3351 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3470

East Asian (EAS) AF: 0.129 AC: 668 AN: 5170

South Asian (SAS) AF: 0.0844 AC: 408 AN: 4832

European-Finnish (FIN) AF: 0.182 AC: 1928 AN: 10604

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10622 AN: 67992

Other (OTH) AF: 0.114 AC: 240 AN: 2114

Alfa AF: 0.143 Hom.: 908

Bravo AF: 0.131

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0060
DANN	Benign	0.36
PhyloP100		-2.8
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: rs5030668; hg19: chr21-46326815; COSMIC: COSV56607815; COSMIC: COSV56607815;