rs35903905

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000211.5(ITGB2):c.117G>A(p.Ser39Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,614,098 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 19 hom., cov: 33)

Exomes 𝑓: 0.016 ( 291 hom. )

Consequence

ITGB2
NM_000211.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0980

Publications

7 publications found

Variant links:

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

ITGB2 links:

LOC107987303 (HGNC:):

LOC107987303 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 21-44910314-C-T is Benign according to our data. Variant chr21-44910314-C-T is described in ClinVar as Benign. ClinVar VariationId is 340180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.098 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0126 (1919/152276) while in subpopulation SAS AF = 0.0435 (210/4828). AF 95% confidence interval is 0.0387. There are 19 homozygotes in GnomAd4. There are 1020 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5 link	c.117G>A	p.Ser39Ser	synonymous_variant	Exon 3 of 16	ENST00000652462.1	NP_000202.3	P05107A0A494C0X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1 link	c.117G>A	p.Ser39Ser	synonymous_variant	Exon 3 of 16		NM_000211.5	ENSP00000498780.1		A0A494C0X7

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1918

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.0353

Gnomad SAS

AF:

0.0433

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.0191

AC:

4785

AN:

251108

AF XY:

0.0210

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.0120

Gnomad EAS exome

AF:

0.0372

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0201

GnomAD4 exome

AF:

0.0162

AC:

23733

AN:

1461822

Hom.:

291

Cov.:

AF XY:

0.0172

AC XY:

12492

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.00191

AC:

AN:

33480

American (AMR)

AF:

0.0109

AC:

488

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

361

AN:

26132

East Asian (EAS)

AF:

0.0369

AC:

1463

AN:

39700

South Asian (SAS)

AF:

0.0443

AC:

3818

AN:

86254

European-Finnish (FIN)

AF:

0.0158

AC:

845

AN:

53394

Middle Eastern (MID)

AF:

0.0220

AC:

127

AN:

5764

European-Non Finnish (NFE)

AF:

0.0140

AC:

15529

AN:

1111988

Other (OTH)

AF:

0.0172

AC:

1038

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

1329

2658

3987

5316

6645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

606

1212

1818

2424

3030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0126

AC:

1919

AN:

152276

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1020

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00260

AC:

108

AN:

41554

American (AMR)

AF:

0.0112

AC:

172

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3472

East Asian (EAS)

AF:

0.0354

AC:

183

AN:

5170

South Asian (SAS)

AF:

0.0435

AC:

210

AN:

4828

European-Finnish (FIN)

AF:

0.0174

AC:

185

AN:

10614

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0144

AC:

979

AN:

68016

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

102

204

305

407

509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0118

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0165

EpiControl

AF:

0.0175

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 1

Benign:2

Jan 12, 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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_noAF

Benign

-0.39

CADD

Benign

4.5

(source)

DANN

Benign

0.90

PhyloP100

-0.098

PromoterAI

-0.0034

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over