rs2230530

Variant names:

• chr21-44890093-G-A
• rs2230530
• NM_000211.5:c.1542C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44890093-G-A
• chr21-44890093-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000211.5(ITGB2):​c.1542C>T​(p.Cys514Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000999 in 1,613,400 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00069 (7 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.464

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 21-44890093-G-A is Benign according to our data. Variant chr21-44890093-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 461472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44890093-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.464 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00397 (605/152202) while in subpopulation EAS AF= 0.0156 (80/5144). AF 95% confidence interval is 0.0128. There are 6 homozygotes in gnomad4. There are 304 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.1542C>T	p.Cys514Cys	synonymous_variant	Exon 12 of 16	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.1542C>T	p.Cys514Cys	synonymous_variant	Exon 12 of 16		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.00397 AC: 604 AN: 152084 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0155

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00206 AC: 518 AN: 251002 Hom.: 5 AF XY: 0.00182 AC XY: 247 AN XY: 135810

Gnomad AFR exome AF: 0.0100

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0139

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000688 AC: 1006 AN: 1461198 Hom.: 7 Cov.: 33 AF XY: 0.000693 AC XY: 504 AN XY: 726910

Gnomad4 AFR exome AF: 0.00923

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00736

Gnomad4 SAS exome AF: 0.000696

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000144

Gnomad4 OTH exome AF: 0.00190

GnomAD4 genome AF: 0.00397 AC: 605 AN: 152202 Hom.: 6 Cov.: 33 AF XY: 0.00409 AC XY: 304 AN XY: 74406

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00134 Hom.: 1

Bravo AF: 0.00403

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000533

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:3

Apr 18, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ITGB2: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.9
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs2230530; hg19: chr21-46310008;