5-53086388-C-G

Position:

• chr5-53086388-C-G

Variant summary

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

The NM_002203.4(ITGA2):​c.3259-564C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,974 control chromosomes in the GnomAD database, including 9,544 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 0.35 (9544 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.3259-564C>G		intron_variant		ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.3259-564C>G		intron_variant		1	NM_002203.4	ENSP00000296585	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53522 AN: 151856 Hom.: 9540 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.352 AC: 53542 AN: 151974 Hom.: 9544 Cov.: 32 AF XY: 0.355 AC XY: 26346 AN XY: 74292

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.359

Alfa AF: 0.373 Hom.: 1328

Bravo AF: 0.351

Asia WGS AF: 0.335 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.58

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: rs12521915; hg19: chr5-52382218;