rs3212657

Positions:

• chr5-52992652-T-C

Variant summary

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

The NM_002203.4(ITGA2):​c.64+3120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,220 control chromosomes in the GnomAD database, including 1,394 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 0.11 (1394 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.64+3120T>C		intron_variant		ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.64+3120T>C		intron_variant		1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17340 AN: 152102 Hom.: 1395 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.114 AC: 17346 AN: 152220 Hom.: 1394 Cov.: 32 AF XY: 0.116 AC XY: 8651 AN XY: 74418

Gnomad4 AFR AF: 0.0495

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0980

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.125

Alfa AF: 0.120 Hom.: 273

Bravo AF: 0.124

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.38

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: rs3212657; hg19: chr5-52288482;