21-44886246-C-T

Variant names:

• chr21-44886246-C-T
• rs684
• NM_000211.5:c.*122G>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.*122G>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 0.204 in 1,002,834 control chromosomes in the GnomAD database, including 22,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3090 hom., cov: 31)
  • Exomes 𝑓: 0.21 (19091 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.420
• Publications: 19 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 21-44886246-C-T is Benign according to our data. Variant chr21-44886246-C-T is described in ClinVar as Benign. ClinVar VariationId is 340134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 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.*122G>A		3_prime_UTR	Exon 16 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.*122G>A		3_prime_UTR	Exon 16 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.*122G>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.*122G>A		3_prime_UTR	Exon 16 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.*122G>A		3_prime_UTR	Exon 17 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.*122G>A		3_prime_UTR	Exon 15 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29765 AN: 151796 Hom.: 3085 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.206 AC: 175103 AN: 850920 Hom.: 19091 Cov.: 11 AF XY: 0.208 AC XY: 92222 AN XY: 444294

African (AFR) AF: 0.160 AC: 3492 AN: 21808

American (AMR) AF: 0.128 AC: 5336 AN: 41752

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 5446 AN: 21940

East Asian (EAS) AF: 0.0923 AC: 3356 AN: 36346

South Asian (SAS) AF: 0.195 AC: 14191 AN: 72950

European-Finnish (FIN) AF: 0.164 AC: 8345 AN: 50758

Middle Eastern (MID) AF: 0.302 AC: 950 AN: 3144

European-Non Finnish (NFE) AF: 0.223 AC: 125541 AN: 562274

Other (OTH) AF: 0.211 AC: 8446 AN: 39948

GnomAD4 genome AF: 0.196 AC: 29778 AN: 151914 Hom.: 3090 Cov.: 31 AF XY: 0.192 AC XY: 14260 AN XY: 74230

African (AFR) AF: 0.162 AC: 6701 AN: 41418

American (AMR) AF: 0.189 AC: 2880 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3472

East Asian (EAS) AF: 0.0840 AC: 433 AN: 5154

South Asian (SAS) AF: 0.189 AC: 909 AN: 4806

European-Finnish (FIN) AF: 0.161 AC: 1694 AN: 10554

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15592 AN: 67930

Other (OTH) AF: 0.223 AC: 471 AN: 2110

Alfa AF: 0.223 Hom.: 3030

Bravo AF: 0.195

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.63
PhyloP100		-0.42
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: rs684; hg19: chr21-46306161; COSMIC: COSV56609304; COSMIC: COSV56609304;