chr21-44888880-G-A

Variant names:

• chr21-44888880-G-A
• rs17004713
• NM_000211.5:c.1893C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000211.5(ITGB2):​c.1893C>T​(p.Cys631Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,605,844 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (80 hom., cov: 34)
  • Exomes 𝑓: 0.0020 (93 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.09
• Publications: 4 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, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 21-44888880-G-A is Benign according to our data. Variant chr21-44888880-G-A is described in ClinVar as Benign. ClinVar VariationId is 340142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.1893C>T	p.Cys631Cys	synonymous	Exon 14 of 16	NP_000202.3
	ITGB2	NM_001127491.3		c.1893C>T	p.Cys631Cys	synonymous	Exon 14 of 16	NP_001120963.2
	ITGB2	NM_001303238.2		c.1686C>T	p.Cys562Cys	synonymous	Exon 14 of 16	NP_001290167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.1893C>T	p.Cys631Cys	synonymous	Exon 14 of 16	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.1965C>T	p.Cys655Cys	synonymous	Exon 15 of 17	ENSP00000303242.6
	ITGB2	ENST00000397852.5	TSL:1	c.1893C>T	p.Cys631Cys	synonymous	Exon 13 of 15	ENSP00000380950.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2765 AN: 152198 Hom.: 79 Cov.: 34

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00480 AC: 1165 AN: 242530 AF XY: 0.00347

Gnomad AFR exome AF: 0.0644

Gnomad AMR exome AF: 0.00322

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000251

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00203 AC: 2945 AN: 1453528 Hom.: 93 Cov.: 33 AF XY: 0.00174 AC XY: 1256 AN XY: 723400

African (AFR) AF: 0.0670 AC: 2244 AN: 33470

American (AMR) AF: 0.00356 AC: 159 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45338

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5762

European-Non Finnish (NFE) AF: 0.000237 AC: 263 AN: 1111846

Other (OTH) AF: 0.00403 AC: 243 AN: 60332

GnomAD4 genome AF: 0.0182 AC: 2770 AN: 152316 Hom.: 80 Cov.: 34 AF XY: 0.0176 AC XY: 1314 AN XY: 74474

African (AFR) AF: 0.0627 AC: 2607 AN: 41572

American (AMR) AF: 0.00706 AC: 108 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68022

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.00801 Hom.: 15

Bravo AF: 0.0205

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000533

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.3
DANN	Benign	0.86
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs17004713; hg19: chr21-46308795;