rs35370671

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr21-44899154-T-C
• chr21-44899154-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.83).
• BP6: Variant 21-44899154-T-C is Benign according to our data. Variant chr21-44899154-T-C is described in ClinVar as Benign. ClinVar VariationId is 340161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.906A>G	p.Pro302Pro	synonymous	Exon 8 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.906A>G	p.Pro302Pro	synonymous	Exon 8 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.699A>G	p.Pro233Pro	synonymous	Exon 8 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.906A>G	p.Pro302Pro	synonymous	Exon 8 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.906A>G	p.Pro302Pro	synonymous	Exon 8 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.906A>G	p.Pro302Pro	synonymous	Exon 7 of 15	ENSP00000380950.1	P05107

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

GnomAD2 exomes AF: 0.0186 AC: 4659 AN: 250688 AF XY: 0.0142

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 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

African (AFR) AF: 0.000986 AC: 33 AN: 33466

American (AMR) AF: 0.116 AC: 5179 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00282 AC: 112 AN: 39694

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86228

European-Finnish (FIN) AF: 0.00800 AC: 427 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1111534

Other (OTH) AF: 0.00374 AC: 226 AN: 60372

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

African (AFR) AF: 0.000938 AC: 39 AN: 41570

American (AMR) AF: 0.0627 AC: 960 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5186

South Asian (SAS) AF: 0.000827 AC: 4 AN: 4834

European-Finnish (FIN) AF: 0.00819 AC: 87 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68018

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00640 Hom.: 36

Bravo AF: 0.0133

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.54
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs35370671; hg19: chr21-46319069;