rs35903905

Positions:

• chr21-44910314-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000211.5(ITGB2):​c.117G>A​(p.Ser39=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0980

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]

LOC107987303 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 340180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44910314-C-T is described in Lovd as [Likely_benign]. Variant chr21-44910314-C-T is described in Lovd as [Benign].
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.117G>A	p.Ser39=	synonymous_variant	3/16	ENST00000652462.1	NP_000202.3
LOC107987303	XR_001755083.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.117G>A	p.Ser39=	synonymous_variant	3/16		NM_000211.5	ENSP00000498780	P1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1918 AN: 152158 Hom.: 19 Cov.: 33

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

GnomAD3 exomes AF: 0.0191 AC: 4785 AN: 251108 Hom.: 74 AF XY: 0.0210 AC XY: 2855 AN XY: 135840

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 SAS exome AF: 0.0451

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.: 32 AF XY: 0.0172 AC XY: 12492 AN XY: 727218

Gnomad4 AFR exome AF: 0.00191

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.0369

Gnomad4 SAS exome AF: 0.0443

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.0140

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0126 AC: 1919 AN: 152276 Hom.: 19 Cov.: 33 AF XY: 0.0137 AC XY: 1020 AN XY: 74440

Gnomad4 AFR AF: 0.00260

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.0354

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0174

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0128 Hom.: 10

Bravo AF: 0.0118

Asia WGS AF: 0.0280 AC: 97 AN: 3478

EpiCase AF: 0.0165

EpiControl AF: 0.0175

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	4.5
DANN	Benign	0.90

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

LitVar

Other links and lift over

dbSNP: rs35903905; hg19: chr21-46330229;