21-44886197-C-G

Variant names:

• chr21-44886197-C-G
• rs6570
• NM_000211.5:c.*171G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000211.5(ITGB2):​c.*171G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 675,362 control chromosomes in the GnomAD database, including 3,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (2668 hom., cov: 32)
  • Exomes 𝑓: 0.014 (1022 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.158
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 21-44886197-C-G is Benign according to our data. Variant chr21-44886197-C-G is described in ClinVar as Benign. ClinVar VariationId is 340129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

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.*171G>C		3_prime_UTR	Exon 16 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.*171G>C		3_prime_UTR	Exon 16 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.*171G>C		3_prime_UTR	Exon 16 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.*171G>C		3_prime_UTR	Exon 16 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.*171G>C		3_prime_UTR	Exon 17 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.*171G>C		3_prime_UTR	Exon 15 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15354 AN: 151980 Hom.: 2661 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.0866

GnomAD4 exome AF: 0.0140 AC: 7312 AN: 523264 Hom.: 1022 Cov.: 6 AF XY: 0.0113 AC XY: 3165 AN XY: 279274

African (AFR) AF: 0.353 AC: 5405 AN: 15298

American (AMR) AF: 0.0201 AC: 652 AN: 32424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17232

East Asian (EAS) AF: 0.0000319 AC: 1 AN: 31390

South Asian (SAS) AF: 0.00118 AC: 66 AN: 55902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35356

Middle Eastern (MID) AF: 0.0146 AC: 33 AN: 2258

European-Non Finnish (NFE) AF: 0.000933 AC: 284 AN: 304536

Other (OTH) AF: 0.0302 AC: 871 AN: 28868

GnomAD4 genome AF: 0.101 AC: 15389 AN: 152098 Hom.: 2668 Cov.: 32 AF XY: 0.0970 AC XY: 7211 AN XY: 74366

African (AFR) AF: 0.350 AC: 14505 AN: 41406

American (AMR) AF: 0.0397 AC: 607 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00119 AC: 81 AN: 68012

Other (OTH) AF: 0.0857 AC: 181 AN: 2112

Alfa AF: 0.00471 Hom.: 6

Bravo AF: 0.118

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leukocyte adhesion deficiency 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.45
PhyloP100		-0.16
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: rs6570; hg19: chr21-46306112;