chr17-44379752-C-T

Position:

chr17-44379752-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4BA1

This summary comes from the ClinGen Evidence Repository: The c.1815G>A variant is a synonymous (silent) variant (p.Pro605=) that is not predicted by SpliceAI to impact splicing (BP4). The highest population minor allele frequency in gnomAD v3.1.2 is 0.03782 (1565/41378 alleles) in African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.0024) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4, BP7. (VCEP specifications version 2; date of approval 4/14/2022) LINK:https://erepo.genome.network/evrepo/ui/classification/CA8602938/MONDO:0010119/011

Frequency

Genomes: 𝑓 0.016 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 75 hom. )

Consequence

ITGA2B
NM_000419.5 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:4

Conservation

PhyloP100: 0.348

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
ITGA2B	NM_000419.5 linkuse as main transcript	c.1815G>A	p.Pro605=	synonymous_variant	18/30	ENST00000262407.6	NP_000410.2
ITGA2B	XM_011524749.2 linkuse as main transcript	c.1968G>A	p.Pro656=	synonymous_variant	18/29		XP_011523051.2
ITGA2B	XM_011524750.2 linkuse as main transcript	c.1968G>A	p.Pro656=	synonymous_variant	18/29		XP_011523052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA2B	ENST00000262407.6 linkuse as main transcript	c.1815G>A	p.Pro605=	synonymous_variant	18/30	1	NM_000419.5	ENSP00000262407	P1	P08514-1
ITGA2B	ENST00000648408.1 linkuse as main transcript	c.1248G>A	p.Pro416=	synonymous_variant	14/25			ENSP00000498119
ITGA2B	ENST00000592462.5 linkuse as main transcript	n.610G>A		non_coding_transcript_exon_variant	7/15	5

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2361

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00757

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00755

AC:

1893

AN:

250740

Hom.:

AF XY:

0.00674

AC XY:

915

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.00735

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.000970

Gnomad NFE exome

AF:

0.00714

Gnomad OTH exome

AF:

0.00898

GnomAD4 exome

AF:

0.00700

AC:

10233

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00678

AC XY:

4929

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.0403

Gnomad4 AMR exome

AF:

0.00852

Gnomad4 ASJ exome

AF:

0.0115

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000684

Gnomad4 FIN exome

AF:

0.00113

Gnomad4 NFE exome

AF:

0.00670

Gnomad4 OTH exome

AF:

0.00879

GnomAD4 genome

AF:

0.0155

AC:

2364

AN:

152118

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1081

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0378

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00758

Gnomad4 OTH

AF:

0.0171

Alfa

AF:

0.00853

Hom.:

Bravo

AF:

0.0183

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00900

EpiControl

AF:

0.00871

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Glanzmann thrombasthenia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, reviewed by expert panel	curation	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	Jun 13, 2022	The c.1815G>A variant is a synonymous (silent) variant (p.Pro605=) that is not predicted by SpliceAI to impact splicing (BP4). The highest population minor allele frequency in gnomAD v3.1.2 is 0.03782 (1565/41378 alleles) in African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.0024) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4, BP7. (VCEP specifications version 2; date of approval 4/14/2022) -

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

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.2

DANN

Benign

0.41

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

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