chr21-44899154-T-C

Variant names:

• chr21-44899154-T-C
• rs35370671
• NM_000211.5:c.906A>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000211.5(ITGB2):​c.906A>G​(p.Pro302Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,613,516 control chromosomes in the GnomAD database, including 461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (49 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (412 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.36

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=-0.83).
• BP6: Variant 21-44899154-T-C is Benign according to our data. Variant chr21-44899154-T-C is described in ClinVar as [Benign]. Clinvar id is 340161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44899154-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.906A>G	p.Pro302Pro	synonymous_variant	Exon 8 of 16	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.906A>G	p.Pro302Pro	synonymous_variant	Exon 8 of 16		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.00746 AC: 1135 AN: 152202 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0627

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00819

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.0186 AC: 4659 AN: 250688 Hom.: 336 AF XY: 0.0142 AC XY: 1931 AN XY: 135642

Gnomad AFR exome AF: 0.000926

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00250

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00858

Gnomad NFE exome AF: 0.000459

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.00424 AC: 6193 AN: 1461196 Hom.: 412 Cov.: 31 AF XY: 0.00366 AC XY: 2658 AN XY: 726940

Gnomad4 AFR exome AF: 0.000986

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00282

Gnomad4 SAS exome AF: 0.000522

Gnomad4 FIN exome AF: 0.00800

Gnomad4 NFE exome AF: 0.000154

Gnomad4 OTH exome AF: 0.00374

GnomAD4 genome AF: 0.00746 AC: 1137 AN: 152320 Hom.: 49 Cov.: 33 AF XY: 0.00891 AC XY: 664 AN XY: 74486

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.0627

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.00819

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00664 Hom.: 36

Bravo AF: 0.0133

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:2

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: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
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.54

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: rs35370671; hg19: chr21-46319069;