chr21-44907920-A-G

Variant names:

• chr21-44907920-A-G
• rs3746972
• NM_000211.5:c.148-825T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000211.5(ITGB2):​c.148-825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 591,072 control chromosomes in the GnomAD database, including 8,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2368 hom., cov: 33)
  • Exomes 𝑓: 0.16 (6325 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206
• Publications: 16 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, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

LOC107987303 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 21-44907920-A-G is Benign according to our data. Variant chr21-44907920-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.148-825T>C		intron_variant	Intron 3 of 15	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.148-825T>C		intron_variant	Intron 3 of 15		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25908 AN: 152170 Hom.: 2371 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.164 AC: 72060 AN: 438784 Hom.: 6325 AF XY: 0.160 AC XY: 37301 AN XY: 232866

African (AFR) AF: 0.127 AC: 1525 AN: 12046

American (AMR) AF: 0.250 AC: 4766 AN: 19092

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 2528 AN: 13774

East Asian (EAS) AF: 0.110 AC: 3280 AN: 29934

South Asian (SAS) AF: 0.0939 AC: 4063 AN: 43288

European-Finnish (FIN) AF: 0.176 AC: 7493 AN: 42514

Middle Eastern (MID) AF: 0.101 AC: 350 AN: 3454

European-Non Finnish (NFE) AF: 0.175 AC: 43851 AN: 250250

Other (OTH) AF: 0.172 AC: 4204 AN: 24432

GnomAD4 genome AF: 0.170 AC: 25913 AN: 152288 Hom.: 2368 Cov.: 33 AF XY: 0.171 AC XY: 12745 AN XY: 74470

African (AFR) AF: 0.131 AC: 5457 AN: 41574

American (AMR) AF: 0.245 AC: 3741 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 640 AN: 3470

East Asian (EAS) AF: 0.135 AC: 702 AN: 5186

South Asian (SAS) AF: 0.0889 AC: 429 AN: 4828

European-Finnish (FIN) AF: 0.184 AC: 1956 AN: 10616

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12285 AN: 67998

Other (OTH) AF: 0.166 AC: 351 AN: 2116

Alfa AF: 0.179 Hom.: 4625

Bravo AF: 0.174

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.64
DANN	Benign	0.68
PhyloP100		-0.21
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: rs3746972; hg19: chr21-46327835; COSMIC: COSV56608886; COSMIC: COSV56608886;