21-44895992-C-T

Variant names:

• chr21-44895992-C-T
• rs2838727
• NM_000211.5:c.994-932G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000211.5(ITGB2):​c.994-932G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,898 control chromosomes in the GnomAD database, including 4,703 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4703 hom., cov: 33)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 6 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 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.994-932G>A		intron	N/A	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.994-932G>A		intron	N/A	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.787-932G>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.994-932G>A		intron	N/A	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.1066-932G>A		intron	N/A	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.994-932G>A		intron	N/A	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36888 AN: 151780 Hom.: 4691 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.275

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 36925 AN: 151898 Hom.: 4703 Cov.: 33 AF XY: 0.240 AC XY: 17847 AN XY: 74232

African (AFR) AF: 0.263 AC: 10876 AN: 41320

American (AMR) AF: 0.216 AC: 3301 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3470

East Asian (EAS) AF: 0.103 AC: 533 AN: 5178

South Asian (SAS) AF: 0.252 AC: 1212 AN: 4818

European-Finnish (FIN) AF: 0.170 AC: 1796 AN: 10560

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17361 AN: 67940

Other (OTH) AF: 0.272 AC: 574 AN: 2108

Alfa AF: 0.124 Hom.: 209

Bravo AF: 0.243

Asia WGS AF: 0.182 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.47
DANN	Benign	0.94
PhyloP100		-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

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

Other links and lift over

dbSNP: rs2838727;

hg19: chr21-46315907;