chr21-44901903-A-T

Variant names:

• chr21-44901903-A-T
• rs1041457
• NM_000211.5:c.500-170T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000211.5(ITGB2):​c.500-170T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 559,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.500-170T>A		intron	N/A	NP_000202.3
	ITGB2	NM_001127491.3		c.500-170T>A		intron	N/A	NP_001120963.2
	ITGB2	NM_001303238.2		c.293-170T>A		intron	N/A	NP_001290167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.500-170T>A		intron	N/A	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.500-170T>A		intron	N/A	ENSP00000303242.6
	ITGB2	ENST00000397852.5	TSL:1	c.500-170T>A		intron	N/A	ENSP00000380950.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000179 AC: 1 AN: 559408 Hom.: 0 AF XY: 0.00000347 AC XY: 1 AN XY: 288460

African (AFR) AF: 0.00 AC: 0 AN: 14504

American (AMR) AF: 0.0000523 AC: 1 AN: 19124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14298

East Asian (EAS) AF: 0.00 AC: 0 AN: 31498

South Asian (SAS) AF: 0.00 AC: 0 AN: 48072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 370268

Other (OTH) AF: 0.00 AC: 0 AN: 29636

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.48
DANN	Benign	0.60
PhyloP100		-1.0

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: rs1041457; hg19: chr21-46321818;