rs989073

chr5-53037590-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002203.4(ITGA2):c.186-4522C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,942 control chromosomes in the GnomAD database, including 7,569 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7569 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA2	NM_002203.4	c.186-4522C>A		intron_variant		ENST00000296585.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA2	ENST00000296585.10	c.186-4522C>A		intron_variant		1	NM_002203.4	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47709 AN: 151824 Hom.: 7566 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.318

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.314 AC: 47739 AN: 151942 Hom.: 7569 Cov.: 32 AF XY: 0.317 AC XY: 23579 AN XY: 74266

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.319

Alfa AF: 0.322 Hom.: 4098

Bravo AF: 0.316

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	7.7
Dann	Benign	0.65

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: rs989073; hg19: chr5-52333420;