21-44900398-C-T

Variant names:

• chr21-44900398-C-T
• rs2230528
• NM_000211.5:c.819G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000211.5(ITGB2):​c.819G>A​(p.Gly273Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,910 control chromosomes in the GnomAD database, including 46,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G273G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.22 (3987 hom., cov: 33)
  • Exomes 𝑓: 0.24 (42057 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:2
• Conservation: PhyloP100: 0.509
• Publications: 23 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 21-44900398-C-T is Benign according to our data. Variant chr21-44900398-C-T is described in ClinVar as Benign. ClinVar VariationId is 100761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.509 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 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.819G>A	p.Gly273Gly	synonymous	Exon 7 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.819G>A	p.Gly273Gly	synonymous	Exon 7 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.612G>A	p.Gly204Gly	synonymous	Exon 7 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.819G>A	p.Gly273Gly	synonymous	Exon 7 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.819G>A	p.Gly273Gly	synonymous	Exon 7 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.819G>A	p.Gly273Gly	synonymous	Exon 6 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33913 AN: 152064 Hom.: 3985 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.226

GnomAD2 exomes AF: 0.247 AC: 61952 AN: 251256 AF XY: 0.247

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.368

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.252

GnomAD4 exome AF: 0.236 AC: 345309 AN: 1461728 Hom.: 42057 Cov.: 38 AF XY: 0.238 AC XY: 173225 AN XY: 727142

African (AFR) AF: 0.167 AC: 5602 AN: 33476

American (AMR) AF: 0.358 AC: 16012 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 6552 AN: 26134

East Asian (EAS) AF: 0.126 AC: 5012 AN: 39696

South Asian (SAS) AF: 0.301 AC: 25957 AN: 86252

European-Finnish (FIN) AF: 0.182 AC: 9721 AN: 53404

Middle Eastern (MID) AF: 0.207 AC: 1196 AN: 5768

European-Non Finnish (NFE) AF: 0.235 AC: 261215 AN: 1111894

Other (OTH) AF: 0.233 AC: 14042 AN: 60390

GnomAD4 genome AF: 0.223 AC: 33917 AN: 152182 Hom.: 3987 Cov.: 33 AF XY: 0.223 AC XY: 16562 AN XY: 74400

African (AFR) AF: 0.170 AC: 7070 AN: 41540

American (AMR) AF: 0.309 AC: 4716 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3470

East Asian (EAS) AF: 0.153 AC: 793 AN: 5170

South Asian (SAS) AF: 0.310 AC: 1493 AN: 4818

European-Finnish (FIN) AF: 0.174 AC: 1842 AN: 10606

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16284 AN: 67978

Other (OTH) AF: 0.224 AC: 473 AN: 2114

Alfa AF: 0.235 Hom.: 6684

Bravo AF: 0.226

Asia WGS AF: 0.244 AC: 848 AN: 3478

EpiCase AF: 0.234

EpiControl AF: 0.246

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Leukocyte adhesion deficiency 1 (4)
-	-	2	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.2
DANN	Benign	0.62
PhyloP100		0.51
Mutation Taster		=99/1	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: rs2230528; hg19: chr21-46320313; COSMIC: COSV56609317; COSMIC: COSV56609317;