17-44380422-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000419.5(ITGA2B):c.1508G>A(p.Ser503Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ITGA2B
NM_000419.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0850

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12393269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2B	NM_000419.5 link	c.1508G>A	p.Ser503Asn	missense_variant	Exon 15 of 30	ENST00000262407.6	NP_000410.2	P08514-1
ITGA2B	XM_011524749.2 link	c.1661G>A	p.Ser554Asn	missense_variant	Exon 15 of 29		XP_011523051.2	P08514
ITGA2B	XM_011524750.2 link	c.1661G>A	p.Ser554Asn	missense_variant	Exon 15 of 29		XP_011523052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGA2B	ENST00000262407.6 link	c.1508G>A	p.Ser503Asn	missense_variant	Exon 15 of 30	1	NM_000419.5	ENSP00000262407.5	P08514-1
ITGA2B	ENST00000648408.1 link	c.938G>A	p.Ser313Asn	missense_variant	Exon 11 of 25			ENSP00000498119.1	A0A3B3IU79
ITGA2B	ENST00000592226.5 link	n.981G>A		non_coding_transcript_exon_variant	Exon 8 of 10	5
ITGA2B	ENST00000592462.5 link	n.303G>A		non_coding_transcript_exon_variant	Exon 4 of 15	5

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251354

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000383

Hom.:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 26, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: ITGA2B c.1508G>A (p.Ser503Asn) results in a conservative amino acid change located in the Integrin alpha Ig-like domain 1 (IPR013649) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251354 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1508G>A has been reported in the literature in individuals affected with ITGA2B-Related Disorders (Jallu_2011). These report(s) do not provide unequivocal conclusions about association of the variant with ITGA2B-Related Disorders. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant. The following publication have been ascertained in the context of this evaluation (PMID: 20723174). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.1

DANN

Benign

0.44

DEOGEN2

Benign

0.054

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.44

M_CAP

Benign

0.0043

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

PrimateAI

Benign

0.30

PROVEAN

Benign

0.47

REVEL

Benign

0.023

Sift

Benign

0.42

Sift4G

Benign

0.72

Polyphen

0.0010

Vest4

0.64

MutPred

0.40

Gain of methylation at K502 (P = 0.1338);

MVP

0.17

MPC

0.27

ClinPred

0.029

GERP RS

1.5

Varity_R

0.22

gMVP

0.16

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