rs1062535

chr5-53055583-G-Achr5-53055583-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002203.4(ITGA2):c.825G>A(p.Thr275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,612,484 control chromosomes in the GnomAD database, including 126,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10606 hom., cov: 32)
  • Exomes 𝑓: 0.40 (115853 hom.)
• Consequence: ITGA2 NM_002203.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.427

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 5-53055583-G-A is Benign according to our data. Variant chr5-53055583-G-A is described in ClinVar as [Benign]. Clinvar id is 353744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-53055583-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.427 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA2	NM_002203.4	c.825G>A	p.Thr275=	synonymous_variant	8/30	ENST00000296585.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA2	ENST00000296585.10	c.825G>A	p.Thr275=	synonymous_variant	8/30	1	NM_002203.4	P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56486 AN: 151744 Hom.: 10601 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.381

GnomAD3 exomes AF: 0.388 AC: 97173 AN: 250348 Hom.: 19154 AF XY: 0.387 AC XY: 52334 AN XY: 135246

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.300

Gnomad SAS exome AF: 0.362

Gnomad FIN exome AF: 0.397

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.396 AC: 578730 AN: 1460620 Hom.: 115853 Cov.: 38 AF XY: 0.395 AC XY: 287134 AN XY: 726640

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.358

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.372 AC: 56517 AN: 151864 Hom.: 10606 Cov.: 32 AF XY: 0.372 AC XY: 27626 AN XY: 74184

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.382

Alfa AF: 0.388 Hom.: 14945

Bravo AF: 0.374

Asia WGS AF: 0.336 AC: 1169 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.387

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Platelet-type bleeding disorder 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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

This variant is associated with the following publications: (PMID: 9950439) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	7.2
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs1062535; hg19: chr5-52351413; COSMIC: COSV56857578;