5-53083447-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002203.4(ITGA2):c.3252C>T(p.Phe1084Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,565,140 control chromosomes in the GnomAD database, including 104,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9326 hom., cov: 32)

Exomes 𝑓: 0.36 ( 95057 hom. )

Consequence

ITGA2
NM_002203.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0620

Publications

27 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 5-53083447-C-T is Benign according to our data. Variant chr5-53083447-C-T is described in ClinVar as Benign. ClinVar VariationId is 353779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.062 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4 link	c.3252C>T	p.Phe1084Phe	synonymous_variant	Exon 27 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.3252C>T	p.Phe1084Phe	synonymous_variant	Exon 27 of 30	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

52932

AN:

151844

Hom.:

9322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.356

GnomAD2 exomes

AF:

0.368

AC:

92207

AN:

250718

AF XY:

0.367

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.445

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.365

AC:

515459

AN:

1413180

Hom.:

95057

Cov.:

AF XY:

0.365

AC XY:

257491

AN XY:

706164

show subpopulations

African (AFR)

AF:

0.285

AC:

9292

AN:

32554

American (AMR)

AF:

0.440

AC:

19636

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

9133

AN:

25830

East Asian (EAS)

AF:

0.365

AC:

14392

AN:

39406

South Asian (SAS)

AF:

0.357

AC:

30440

AN:

85254

European-Finnish (FIN)

AF:

0.392

AC:

20916

AN:

53342

Middle Eastern (MID)

AF:

0.339

AC:

1916

AN:

5656

European-Non Finnish (NFE)

AF:

0.364

AC:

388505

AN:

1067730

Other (OTH)

AF:

0.361

AC:

21229

AN:

58782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

15481

30962

46444

61925

77406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12106

24212

36318

48424

60530

<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:

0.348

AC:

52951

AN:

151960

Hom.:

9326

Cov.:

AF XY:

0.351

AC XY:

26052

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.285

AC:

11825

AN:

41432

American (AMR)

AF:

0.412

AC:

6289

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1183

AN:

3470

East Asian (EAS)

AF:

0.314

AC:

1620

AN:

5166

South Asian (SAS)

AF:

0.347

AC:

1672

AN:

4820

European-Finnish (FIN)

AF:

0.395

AC:

4171

AN:

10552

Middle Eastern (MID)

AF:

0.334

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.368

AC:

24971

AN:

67944

Other (OTH)

AF:

0.356

AC:

752

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1791

3582

5374

7165

8956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.359

Hom.:

35044

Bravo

AF:

0.348

Asia WGS

AF:

0.334

AC:

1162

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Platelet-type bleeding disorder 9

Benign:1

Jan 13, 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

-0.39

CADD

Benign

0.81

(source)

DANN

Benign

0.50

PhyloP100

0.062

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