Variant 5-53083447-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002203.4(ITGA2):c.3252C>T(p.Phe1084=) 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:2

Conservation

PhyloP100: 0.0620

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 353779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-53083447-C-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
ITGA2	NM_002203.4 linkuse as main transcript	c.3252C>T	p.Phe1084=	synonymous_variant	27/30	ENST00000296585.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA2	ENST00000296585.10 linkuse as main transcript	c.3252C>T	p.Phe1084=	synonymous_variant	27/30	1	NM_002203.4	P1

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

GnomAD3 exomes

AF:

0.368

AC:

92207

AN:

250718

Hom.:

17274

AF XY:

0.367

AC XY:

49676

AN XY:

135476

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 SAS exome

AF:

0.355

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

Gnomad4 AFR exome

AF:

0.285

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.365

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.392

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.361

GnomAD4 genome

AF:

0.348

AC:

52951

AN:

151960

Hom.:

9326

Cov.:

AF XY:

0.351

AC XY:

26052

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.412

Gnomad4 ASJ

AF:

0.341

Gnomad4 EAS

AF:

0.314

Gnomad4 SAS

AF:

0.347

Gnomad4 FIN

AF:

0.395

Gnomad4 NFE

AF:

0.368

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.360

Hom.:

23255

Bravo

AF:

0.348

Asia WGS

AF:

0.334

AC:

1162

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Platelet-type bleeding disorder 9

Benign:1

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:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.81

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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