5-53051539-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BA1

The NM_002203.4(ITGA2):c.759C>T(p.Phe253Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,611,596 control chromosomes in the GnomAD database, including 124,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10259 hom., cov: 31)

Exomes 𝑓: 0.39 ( 114694 hom. )

Consequence

ITGA2
NM_002203.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.61

Publications

161 publications found

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 Gene-Disease associations (from GenCC):

platelet-type bleeding disorder 9
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ITGA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.15).

BP6

Variant 5-53051539-C-T is Benign according to our data. Variant chr5-53051539-C-T is described in ClinVar as Benign. ClinVar VariationId is 353741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4 link	c.759C>T	p.Phe253Phe	synonymous_variant	Exon 7 of 30	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10 link	c.759C>T	p.Phe253Phe	synonymous_variant	Exon 7 of 30	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55405

AN:

151598

Hom.:

10260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.374

GnomAD2 exomes

AF:

0.386

AC:

96856

AN:

250968

AF XY:

0.385

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.396

Gnomad NFE exome

AF:

0.397

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

AF:

0.394

AC:

575320

AN:

1459880

Hom.:

114694

Cov.:

AF XY:

0.393

AC XY:

285560

AN XY:

726314

show subpopulations

African (AFR)

AF:

0.289

AC:

9651

AN:

33414

American (AMR)

AF:

0.453

AC:

20237

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

9917

AN:

26098

East Asian (EAS)

AF:

0.358

AC:

14200

AN:

39616

South Asian (SAS)

AF:

0.365

AC:

31482

AN:

86218

European-Finnish (FIN)

AF:

0.396

AC:

21176

AN:

53414

Middle Eastern (MID)

AF:

0.371

AC:

2139

AN:

5758

European-Non Finnish (NFE)

AF:

0.399

AC:

443149

AN:

1110344

Other (OTH)

AF:

0.387

AC:

23369

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

17730

35459

53189

70918

88648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13746

27492

41238

54984

68730

<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:

0.365

AC:

55426

AN:

151716

Hom.:

10259

Cov.:

AF XY:

0.366

AC XY:

27111

AN XY:

74128

show subpopulations

African (AFR)

AF:

0.290

AC:

11990

AN:

41358

American (AMR)

AF:

0.428

AC:

6515

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1265

AN:

3470

East Asian (EAS)

AF:

0.305

AC:

1572

AN:

5150

South Asian (SAS)

AF:

0.352

AC:

1687

AN:

4794

European-Finnish (FIN)

AF:

0.396

AC:

4166

AN:

10508

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.397

AC:

26955

AN:

67898

Other (OTH)

AF:

0.375

AC:

788

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1768

3535

5303

7070

8838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<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:

0.387

Hom.:

41618

Bravo

AF:

0.366

Asia WGS

AF:

0.335

AC:

1165

AN:

3476

EpiCase

AF:

0.393

EpiControl

AF:

0.386

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 9950439, 22133274, 21672359, 18836731, 14687991, 16513317, 19388931) -

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

BayesDel_noAF

Benign

-0.15

CADD

Benign

7.8

(source)

DANN

Benign

0.82

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over