21-44907048-C-G

Variant names:

• chr21-44907048-C-G
• rs149429459
• NM_000211.5:c.195G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_000211.5(ITGB2):​c.195G>C​(p.Arg65Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000906 in 1,612,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R65R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: ITGB2 NM_000211.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.15
• 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 21-44907048-C-G is Benign according to our data. Variant chr21-44907048-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 785779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.15 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000532 (81/152232) while in subpopulation AFR AF = 0.00188 (78/41532). AF 95% confidence interval is 0.00154. There are 0 homozygotes in GnomAd4. There are 35 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.195G>C	p.Arg65Arg	synonymous	Exon 4 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.195G>C	p.Arg65Arg	synonymous	Exon 4 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.-13G>C		5_prime_UTR	Exon 4 of 16	NP_001290167.1	B4E0R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.195G>C	p.Arg65Arg	synonymous	Exon 4 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.195G>C	p.Arg65Arg	synonymous	Exon 4 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.195G>C	p.Arg65Arg	synonymous	Exon 3 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.000532 AC: 81 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000131 AC: 33 AN: 250972 AF XY: 0.0000958

Gnomad AFR exome AF: 0.00203

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000445 AC: 65 AN: 1460030 Hom.: 0 Cov.: 32 AF XY: 0.0000441 AC XY: 32 AN XY: 725960

African (AFR) AF: 0.00167 AC: 56 AN: 33452

American (AMR) AF: 0.0000447 AC: 2 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110600

Other (OTH) AF: 0.0000829 AC: 5 AN: 60300

GnomAD4 genome AF: 0.000532 AC: 81 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74434

African (AFR) AF: 0.00188 AC: 78 AN: 41532

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000578

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leukocyte adhesion deficiency 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs149429459; hg19: chr21-46326963;