rs760462

Variant names:

• chr21-44908184-T-A
• rs760462
• NM_000211.5:c.148-1089A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44908184-T-A
• chr21-44908184-T-C

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.148-1089A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITGB2 NM_000211.5 intron
• Scores: Splicing: ADA: 0.00002529
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48
• Publications: 42 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: 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_addAF=-0.455999).

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.148-1089A>T		intron	N/A	NP_000202.3
	ITGB2	NM_001127491.3		c.148-1089A>T		intron	N/A	NP_001120963.2
	ITGB2	NM_001303238.2		c.-60-1089A>T		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.148-1089A>T		intron	N/A	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.148-1089A>T		intron	N/A	ENSP00000303242.6
	ITGB2	ENST00000397852.5	TSL:1	c.148-1089A>T		intron	N/A	ENSP00000380950.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000539 AC: 1 AN: 185526 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 567504 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 306556

African (AFR) AF: 0.00 AC: 0 AN: 16162

American (AMR) AF: 0.00 AC: 0 AN: 34644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19160

East Asian (EAS) AF: 0.00 AC: 0 AN: 34224

South Asian (SAS) AF: 0.00 AC: 0 AN: 62936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3896

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 316990

Other (OTH) AF: 0.00 AC: 0 AN: 30344

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.34
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0030	N
PhyloP100		-3.5
GERP RS		-2.3
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
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: rs760462; hg19: chr21-46328099;