rs3212441

Positions:

• chr5-53042078-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002203.4(ITGA2):​c.186-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,215,734 control chromosomes in the GnomAD database, including 49,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5809 hom., cov: 32)
  • Exomes 𝑓: 0.28 (43863 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.89

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-53042078-C-T is Benign according to our data. Variant chr5-53042078-C-T is described in ClinVar as [Benign]. Clinvar id is 1277882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.186-34C>T		intron_variant		ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.186-34C>T		intron_variant		1	NM_002203.4	ENSP00000296585	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41737 AN: 151880 Hom.: 5808 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.272

GnomAD3 exomes AF: 0.291 AC: 72927 AN: 250482 Hom.: 10839 AF XY: 0.290 AC XY: 39252 AN XY: 135422

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.230

Gnomad SAS exome AF: 0.298

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.284 AC: 301589 AN: 1063738 Hom.: 43863 Cov.: 14 AF XY: 0.284 AC XY: 155329 AN XY: 547802

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.275 AC: 41760 AN: 151996 Hom.: 5809 Cov.: 32 AF XY: 0.278 AC XY: 20653 AN XY: 74266

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.273

Alfa AF: 0.282 Hom.: 1355

Bravo AF: 0.273

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs3212441; hg19: chr5-52337908; COSMIC: COSV56857556;