rs5913

Positions:

• chr17-44374686-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP7 BA1 BP4

This summary comes from the ClinGen Evidence Repository: The c.2916G>A; p.Pro972= synonymous variant has not been reported in the literature to our knowledge. It is present in a non-Finnish European control population at an allele frequency of 0.005351 and no splice impact is predicted. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1, BP4, and BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8602530/MONDO:0010119/011

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (22 hom.)
• Consequence: ITGA2B NM_000419.5 synonymous
• Clinical Significance: Benign reviewed by expert panel B:6
• Conservation: PhyloP100: -0.432

Genes affected

ITGA2B (HGNC:6138): (integrin subunit alpha 2b) This gene encodes a member of the integrin alpha chain family of proteins. The encoded preproprotein is proteolytically processed to generate light and heavy chains that associate through disulfide linkages to form a subunit of the alpha-IIb/beta-3 integrin cell adhesion receptor. This receptor plays a crucial role in the blood coagulation system, by mediating platelet aggregation. Mutations in this gene are associated with platelet-type bleeding disorders, which are characterized by a failure of platelet aggregation, including Glanzmann thrombasthenia. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BP7: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA2B	NM_000419.5	c.2916G>A	p.Pro972=	synonymous_variant	28/30	ENST00000262407.6	NP_000410.2
ITGA2B	XM_011524750.2	c.3069G>A	p.Pro1023=	synonymous_variant	28/29		XP_011523052.2
ITGA2B	XM_011524749.2	c.2995-216G>A		intron_variant			XP_011523051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA2B	ENST00000262407.6	c.2916G>A	p.Pro972=	synonymous_variant	28/30	1	NM_000419.5	ENSP00000262407	P1
ITGA2B	ENST00000648408.1	c.2349G>A	p.Pro783=	synonymous_variant	24/25			ENSP00000498119
ITGA2B	ENST00000587295.5	c.253+1147G>A		intron_variant		3		ENSP00000467269
ITGA2B	ENST00000592462.5	n.2427G>A		non_coding_transcript_exon_variant	15/15	5

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 514 AN: 152080 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00634

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00291 AC: 729 AN: 250896 Hom.: 4 AF XY: 0.00305 AC XY: 414 AN XY: 135702

Gnomad AFR exome AF: 0.000864

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.000556

Gnomad NFE exome AF: 0.00550

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00470 AC: 6863 AN: 1461676 Hom.: 22 Cov.: 31 AF XY: 0.00459 AC XY: 3339 AN XY: 727142

Gnomad4 AFR exome AF: 0.000866

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.000731

Gnomad4 NFE exome AF: 0.00581

Gnomad4 OTH exome AF: 0.00315

GnomAD4 genome AF: 0.00338 AC: 514 AN: 152198 Hom.: 4 Cov.: 32 AF XY: 0.00285 AC XY: 212 AN XY: 74400

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00634

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00509 Hom.: 1

Bravo AF: 0.00355

EpiCase AF: 0.00703

EpiControl AF: 0.00646

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: reviewed by expert panel

Submissions by phenotype

Glanzmann thrombasthenia Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	May 07, 2021	The c.2916G>A; p.Pro972= synonymous variant has not been reported in the literature to our knowledge. It is present in a non-Finnish European control population at an allele frequency of 0.005351 and no splice impact is predicted. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1, BP4, and BP7. -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ITGA2B: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.8
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs5913; hg19: chr17-42452054;