rs2910964

Positions:

• chr5-53054691-G-A

Variant summary

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

The NM_002203.4(ITGA2):​c.780-847G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,908 control chromosomes in the GnomAD database, including 10,200 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 0.36 (10200 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.780-847G>A		intron_variant		ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.780-847G>A		intron_variant		1	NM_002203.4	ENSP00000296585	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55164 AN: 151790 Hom.: 10201 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.363 AC: 55185 AN: 151908 Hom.: 10200 Cov.: 32 AF XY: 0.364 AC XY: 26996 AN XY: 74214

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.373

Alfa AF: 0.388 Hom.: 2118

Bravo AF: 0.364

Asia WGS AF: 0.333 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.35

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: rs2910964; hg19: chr5-52350521;