chr21-44900410-G-A

Variant names:

• chr21-44900410-G-A
• rs142381225
• NM_000211.5:c.807C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000211.5(ITGB2):​c.807C>T​(p.Phe269Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000427 in 1,614,062 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.163
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 21-44900410-G-A is Benign according to our data. Variant chr21-44900410-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 530691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.163 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00222 (338/152306) while in subpopulation AFR AF = 0.00724 (301/41576). AF 95% confidence interval is 0.00657. There are 3 homozygotes in GnomAd4. There are 181 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.807C>T	p.Phe269Phe	synonymous	Exon 7 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.807C>T	p.Phe269Phe	synonymous	Exon 7 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.600C>T	p.Phe200Phe	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.807C>T	p.Phe269Phe	synonymous	Exon 7 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.807C>T	p.Phe269Phe	synonymous	Exon 7 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.807C>T	p.Phe269Phe	synonymous	Exon 6 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 337 AN: 152188 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.000545 AC: 137 AN: 251284 AF XY: 0.000486

Gnomad AFR exome AF: 0.00739

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000240 AC: 351 AN: 1461756 Hom.: 2 Cov.: 33 AF XY: 0.000204 AC XY: 148 AN XY: 727162

African (AFR) AF: 0.00768 AC: 257 AN: 33480

American (AMR) AF: 0.000537 AC: 24 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111922

Other (OTH) AF: 0.000613 AC: 37 AN: 60392

GnomAD4 genome AF: 0.00222 AC: 338 AN: 152306 Hom.: 3 Cov.: 33 AF XY: 0.00243 AC XY: 181 AN XY: 74464

African (AFR) AF: 0.00724 AC: 301 AN: 41576

American (AMR) AF: 0.00196 AC: 30 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00285 AC: 6 AN: 2106

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.00283

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Leukocyte adhesion deficiency 1 (2)
-	-	1	ITGB2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		-0.16
Mutation Taster		=99/1	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: rs142381225; hg19: chr21-46320325; COSMIC: COSV56610201; COSMIC: COSV56610201;