21-44920928-A-C

Variant names:

• chr21-44920928-A-C
• rs2070947
• ENST00000498666.5:n.33T>G

Variant summary

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

The NM_001127491.3(ITGB2):​c.-4+7726T>G 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: 32)
• Consequence: ITGB2 NM_001127491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 18 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-AS1 (HGNC:44304): (ITGB2 antisense RNA 1)

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=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127491.3. 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_001127491.3		c.-4+7726T>G		intron	N/A	NP_001120963.2
	ITGB2	NM_000211.5	MANE Select	c.-111T>G		upstream_gene	N/A	NP_000202.3
	ITGB2	NM_001303238.2		c.-361T>G		upstream_gene	N/A	NP_001290167.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000498666.5	TSL:1	n.33T>G		non_coding_transcript_exon	Exon 1 of 15
	ITGB2	ENST00000397850.6	TSL:5	c.-111T>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	ENSP00000380948.2
	ITGB2	ENST00000517563.5	TSL:4	c.-111T>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000428413.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.40
PhyloP100		0.32
PromoterAI		-0.22	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2070947; hg19: chr21-46340843;