rs9983887

Variant names:

• chr21-44903541-G-A
• rs9983887
• NM_000211.5:c.329-6C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44903541-G-A
• chr21-44903541-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000211.5(ITGB2):​c.329-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,613,896 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (21 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (16 hom.)
• Consequence: ITGB2 NM_000211.5 splice_region, intron
• Scores: Splicing: ADA: 0.00002478
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.81

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 21-44903541-G-A is Benign according to our data. Variant chr21-44903541-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 100754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44903541-G-A is described in Lovd as [Likely_benign]. Variant chr21-44903541-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00803 (1223/152280) while in subpopulation AFR AF= 0.0279 (1160/41552). AF 95% confidence interval is 0.0266. There are 21 homozygotes in gnomad4. There are 598 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.329-6C>T		splice_region_variant, intron_variant	Intron 4 of 15	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.329-6C>T		splice_region_variant, intron_variant	Intron 4 of 15		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.00802 AC: 1221 AN: 152162 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00862

GnomAD3 exomes AF: 0.00210 AC: 526 AN: 250106 Hom.: 6 AF XY: 0.00168 AC XY: 228 AN XY: 135366

Gnomad AFR exome AF: 0.0303

Gnomad AMR exome AF: 0.000666

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000799

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000790 AC: 1155 AN: 1461616 Hom.: 16 Cov.: 32 AF XY: 0.000674 AC XY: 490 AN XY: 727142

Gnomad4 AFR exome AF: 0.0285

Gnomad4 AMR exome AF: 0.000738

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000549

Gnomad4 OTH exome AF: 0.00156

GnomAD4 genome AF: 0.00803 AC: 1223 AN: 152280 Hom.: 21 Cov.: 33 AF XY: 0.00803 AC XY: 598 AN XY: 74456

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00516 Hom.: 2

Bravo AF: 0.00899

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:4

May 28, 2019

Mendelics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 30, 2023

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: not provided

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.65
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.050		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: rs9983887; hg19: chr21-46323456;