chr17-44372421-G-A

Position:

chr17-44372421-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000419.5(ITGA2B):c.3063C>T(p.Val1021=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,611,870 control chromosomes in the GnomAD database, including 115,978 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11415 hom., cov: 30)

Exomes 𝑓: 0.38 ( 104563 hom. )

Consequence

ITGA2B
NM_000419.5 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.87

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-44372421-G-A is Benign according to our data. Variant chr17-44372421-G-A is described in ClinVar as [Benign]. Clinvar id is 256040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ITGA2B	NM_000419.5 linkuse as main transcript	c.3063C>T	p.Val1021=	splice_region_variant, synonymous_variant	30/30	ENST00000262407.6
ITGA2B	XM_011524749.2 linkuse as main transcript	c.3114C>T	p.Val1038=	splice_region_variant, synonymous_variant	29/29
ITGA2B	XM_011524750.2 linkuse as main transcript	c.3099C>T	p.Val1033=	splice_region_variant, synonymous_variant	29/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA2B	ENST00000262407.6 linkuse as main transcript	c.3063C>T	p.Val1021=	splice_region_variant, synonymous_variant	30/30	1	NM_000419.5	P1	P08514-1
ITGA2B	ENST00000648408.1 linkuse as main transcript	c.2379C>T	p.Val793=	splice_region_variant, synonymous_variant	25/25
ITGA2B	ENST00000587295.5 linkuse as main transcript	c.258C>T	p.Val86=	splice_region_variant, synonymous_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58721

AN:

151574

Hom.:

11419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.363

GnomAD3 exomes

AF:

0.388

AC:

97222

AN:

250774

Hom.:

18940

AF XY:

0.383

AC XY:

51946

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.430

Gnomad SAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.383

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.378

AC:

551269

AN:

1460176

Hom.:

104563

Cov.:

AF XY:

0.376

AC XY:

272986

AN XY:

726520

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.374

Gnomad4 ASJ exome

AF:

0.426

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.346

Gnomad4 FIN exome

AF:

0.432

Gnomad4 NFE exome

AF:

0.375

Gnomad4 OTH exome

AF:

0.381

GnomAD4 genome

AF:

0.387

AC:

58734

AN:

151694

Hom.:

11415

Cov.:

AF XY:

0.387

AC XY:

28671

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.389

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.437

Gnomad4 EAS

AF:

0.439

Gnomad4 SAS

AF:

0.353

Gnomad4 FIN

AF:

0.435

Gnomad4 NFE

AF:

0.384

Gnomad4 OTH

AF:

0.360

Alfa

AF:

0.376

Hom.:

15095

Bravo

AF:

0.380

Asia WGS

AF:

0.402

AC:

1406

AN:

3478

EpiCase

AF:

0.380

EpiControl

AF:

0.367

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glanzmann thrombasthenia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Glanzmann thrombasthenia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0070

DANN

Benign

0.84

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