chr21-44886223-G-T

Variant names:

• chr21-44886223-G-T
• rs1160263
• NM_000211.5:c.*145C>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.*145C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 802,898 control chromosomes in the GnomAD database, including 13,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1840 hom., cov: 32)
  • Exomes 𝑓: 0.18 (11727 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.227
• Publications: 11 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=-0.87).
• BP6: Variant 21-44886223-G-T is Benign according to our data. Variant chr21-44886223-G-T is described in ClinVar as Benign. ClinVar VariationId is 340133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 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.*145C>A		3_prime_UTR	Exon 16 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.*145C>A		3_prime_UTR	Exon 16 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.*145C>A		3_prime_UTR	Exon 16 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.*145C>A		3_prime_UTR	Exon 16 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.*145C>A		3_prime_UTR	Exon 17 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.*145C>A		3_prime_UTR	Exon 15 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20787 AN: 151924 Hom.: 1834 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0959

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.183 AC: 118858 AN: 650856 Hom.: 11727 Cov.: 9 AF XY: 0.187 AC XY: 64844 AN XY: 346014

African (AFR) AF: 0.0344 AC: 618 AN: 17968

American (AMR) AF: 0.0878 AC: 3188 AN: 36318

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 2616 AN: 19960

East Asian (EAS) AF: 0.230 AC: 7789 AN: 33862

South Asian (SAS) AF: 0.263 AC: 17292 AN: 65742

European-Finnish (FIN) AF: 0.201 AC: 8995 AN: 44726

Middle Eastern (MID) AF: 0.159 AC: 412 AN: 2594

European-Non Finnish (NFE) AF: 0.182 AC: 72191 AN: 396418

Other (OTH) AF: 0.173 AC: 5757 AN: 33268

GnomAD4 genome AF: 0.137 AC: 20801 AN: 152042 Hom.: 1840 Cov.: 32 AF XY: 0.140 AC XY: 10386 AN XY: 74294

African (AFR) AF: 0.0361 AC: 1498 AN: 41496

American (AMR) AF: 0.0958 AC: 1464 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1173 AN: 5170

South Asian (SAS) AF: 0.279 AC: 1342 AN: 4808

European-Finnish (FIN) AF: 0.201 AC: 2121 AN: 10536

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12335 AN: 67962

Other (OTH) AF: 0.141 AC: 298 AN: 2116

Alfa AF: 0.0915 Hom.: 222

Bravo AF: 0.124

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.46
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1160263; hg19: chr21-46306138; COSMIC: COSV56609771; COSMIC: COSV56609771;