rs7207402

Positions:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BP4

This summary comes from the ClinGen Evidence Repository: The NM_000419.5:c.1945G>T (p.Val649Leu) variant occurs at an allele frequency of 0.01773 in the gnomAD African population and is predicted by REVEL score of 0.035 to have no impact. In summary, the variant is classified as benign. GT-specific criteria applied: BA1 and BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8602902/MONDO:0010119/011

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 7 hom. )

Consequence

ITGA2B
NM_000419.5 missense, splice_region

Scores

Splicing: ADA: 0.001055

Clinical Significance

Benign reviewed by expert panel B:5

Conservation

PhyloP100: -0.347

Variant links:

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]

ITGA2B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

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 link	c.1945G>T	p.Val649Leu	missense_variant, splice_region_variant	19/30	ENST00000262407.6	NP_000410.2	P08514-1
ITGA2B	XM_011524749.2 link	c.2098G>T	p.Val700Leu	missense_variant, splice_region_variant	19/29		XP_011523051.2	P08514
ITGA2B	XM_011524750.2 link	c.2098G>T	p.Val700Leu	missense_variant, splice_region_variant	19/29		XP_011523052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITGA2B	ENST00000262407.6 link	c.1945G>T	p.Val649Leu	missense_variant, splice_region_variant	19/30	1	NM_000419.5	ENSP00000262407.5	P08514-1
ITGA2B	ENST00000648408.1 link	c.1375G>T	p.Val459Leu	missense_variant, splice_region_variant	15/25			ENSP00000498119.1	A0A3B3IU79
ITGA2B	ENST00000592462.5 link	n.740G>T		splice_region_variant, non_coding_transcript_exon_variant	8/15	5

Frequencies

GnomAD3 genomes

AF:

0.00445

AC:

678

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00115

AC:

201

AN:

174878

Hom.:

AF XY:

0.000963

AC XY:

AN XY:

92436

show subpopulations

Gnomad AFR exome

AF:

0.0173

Gnomad AMR exome

AF:

0.000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000126

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000419

GnomAD4 exome

AF:

0.000451

AC:

638

AN:

1414096

Hom.:

Cov.:

AF XY:

0.000412

AC XY:

288

AN XY:

698760

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.000544

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000746

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000110

Gnomad4 OTH exome

AF:

0.000887

GnomAD4 genome

AF:

0.00444

AC:

677

AN:

152322

Hom.:

Cov.:

AF XY:

0.00436

AC XY:

325

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0157

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000588

Hom.:

Bravo

AF:

0.00512

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00123

AC:

146

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Glanzmann thrombasthenia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	Jun 04, 2020	The NM_000419.5:c.1945G>T (p.Val649Leu) variant occurs at an allele frequency of 0.01773 in the gnomAD African population and is predicted by REVEL score of 0.035 to have no impact. In summary, the variant is classified as benign. GT-specific criteria applied: BA1 and BP4. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 02, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.3

DANN

Benign

0.58

DEOGEN2

Benign

0.060

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.71

REVEL

Benign

0.035

Sift

Benign

0.70

Sift4G

Benign

0.69

Polyphen

0.038

Vest4

0.051

MutPred

0.25

Loss of catalytic residue at V649 (P = 0.0903);

MVP

0.19

MPC

0.29

ClinPred

0.0037

GERP RS

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0011

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over