chr5-53062927-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002203.4(ITGA2):c.1600G>A(p.Glu534Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 1,598,154 control chromosomes in the GnomAD database, including 7,290 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1140 hom., cov: 32)

Exomes 𝑓: 0.088 ( 6150 hom. )

Consequence

ITGA2
NM_002203.4 missense, splice_region

Scores

Splicing: ADA: 0.00001115

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.00

Variant links:

Genes affected

ITGA2 (HGNC:6137): (integrin subunit alpha 2) This gene encodes the alpha subunit of a transmembrane receptor for collagens and related proteins. The encoded protein forms a heterodimer with a beta subunit and mediates the adhesion of platelets and other cell types to the extracellular matrix. Loss of the encoded protein is associated with bleeding disorder platelet-type 9. Antibodies against this protein are found in several immune disorders, including neonatal alloimmune thrombocytopenia. This gene is located adjacent to a related alpha subunit gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ITGA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011746883).

BP6

Variant 5-53062927-G-A is Benign according to our data. Variant chr5-53062927-G-A is described in ClinVar as [Benign]. Clinvar id is 353753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4 link	c.1600G>A	p.Glu534Lys	missense_variant, splice_region_variant	Exon 13 of 30	ENST00000296585.10	NP_002194.2	P17301

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10 link	c.1600G>A	p.Glu534Lys	missense_variant, splice_region_variant	Exon 13 of 30	1	NM_002203.4	ENSP00000296585.5		P17301

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

16833

AN:

149358

Hom.:

1132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0850

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.0269

Gnomad SAS

AF:

0.0873

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.159

Gnomad NFE

AF:

0.0903

Gnomad OTH

AF:

0.124

GnomAD2 exomes

AF:

0.0856

AC:

20898

AN:

244036

AF XY:

0.0867

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.0597

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.0193

Gnomad FIN exome

AF:

0.0540

Gnomad NFE exome

AF:

0.0914

Gnomad OTH exome

AF:

0.0961

GnomAD4 exome

AF:

0.0877

AC:

127055

AN:

1448680

Hom.:

6150

Cov.:

AF XY:

0.0883

AC XY:

63645

AN XY:

720734

show subpopulations

Gnomad4 AFR exome

AF:

0.193

AC:

6340

AN:

32862

Gnomad4 AMR exome

AF:

0.0621

AC:

2712

AN:

43658

Gnomad4 ASJ exome

AF:

0.115

AC:

2968

AN:

25796

Gnomad4 EAS exome

AF:

0.0338

AC:

1330

AN:

39324

Gnomad4 SAS exome

AF:

0.0896

AC:

7600

AN:

84826

Gnomad4 FIN exome

AF:

0.0531

AC:

2814

AN:

52982

Gnomad4 NFE exome

AF:

0.0876

AC:

96716

AN:

1103902

Gnomad4 Remaining exome

AF:

0.0956

AC:

5705

AN:

59650

Heterozygous variant carriers

4898

9796

14693

19591

24489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

3536

7072

10608

14144

17680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.113

AC:

16880

AN:

149474

Hom.:

1140

Cov.:

AF XY:

0.109

AC XY:

7943

AN XY:

72770

show subpopulations

Gnomad4 AFR

AF:

0.188

AC:

0.188009

AN:

0.188009

Gnomad4 AMR

AF:

0.0849

AC:

0.0848731

AN:

0.0848731

Gnomad4 ASJ

AF:

0.112

AC:

0.111949

AN:

0.111949

Gnomad4 EAS

AF:

0.0269

AC:

0.0269414

AN:

0.0269414

Gnomad4 SAS

AF:

0.0873

AC:

0.0872582

AN:

0.0872582

Gnomad4 FIN

AF:

0.0587

AC:

0.0586558

AN:

0.0586558

Gnomad4 NFE

AF:

0.0903

AC:

0.0903106

AN:

0.0903106

Gnomad4 OTH

AF:

0.125

AC:

0.125242

AN:

0.125242

Heterozygous variant carriers

755

1510

2266

3021

3776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0938

Hom.:

2661

Bravo

AF:

0.117

TwinsUK

AF:

0.0903

AC:

335

ALSPAC

AF:

0.0919

AC:

354

ESP6500AA

AF:

0.181

AC:

799

ESP6500EA

AF:

0.0957

AC:

823

ExAC

AF:

0.0875

AC:

10605

Asia WGS

AF:

0.0890

AC:

308

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22133774, 7901236, 10744142) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Platelet-type bleeding disorder 9

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.83

Eigen

Benign

0.00062

Eigen_PC

Benign

0.025

FATHMM_MKL

Benign

0.38

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.39

PROVEAN

Benign

0.59

REVEL

Benign

0.057

Sift

Benign

0.88

Sift4G

Benign

1.0

Vest4

0.044

MPC

0.19

ClinPred

0.0059

GERP RS

4.8

gMVP

0.54

Mutation Taster

=96/4

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000011

dbscSNV1_RF

Benign

0.0

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