rs35903905

Variant names:

• chr21-44910314-C-T
• rs35903905
• NM_000211.5:c.117G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0980
• Publications: 7 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

LOC107987303 (HGNC:):

ACMG classification

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

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.117G>A	p.Ser39Ser	synonymous	Exon 3 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.117G>A	p.Ser39Ser	synonymous	Exon 3 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.-91G>A		5_prime_UTR	Exon 3 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.117G>A	p.Ser39Ser	synonymous	Exon 3 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.117G>A	p.Ser39Ser	synonymous	Exon 3 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.117G>A	p.Ser39Ser	synonymous	Exon 2 of 15	ENSP00000380950.1	P05107

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

GnomAD2 exomes AF: 0.0191 AC: 4785 AN: 251108 AF XY: 0.0210

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

African (AFR) AF: 0.00191 AC: 64 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

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

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: 40 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: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 979 AN: 68016

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

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

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
AlphaMissense	Uncertain	0.35
BayesDel_noAF	Benign	-0.39
CADD	Benign	4.5
DANN	Benign	0.90
PhyloP100		-0.098
PromoterAI		-0.0034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35903905; hg19: chr21-46330229; COSMIC: COSV107332586; COSMIC: COSV107332586;