rs4865756

Positions:

• chr5-53017734-G-A
• chr5-53017734-G-C

Variant summary

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

The NM_002203.4(ITGA2):​c.65-9014G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,032 control chromosomes in the GnomAD database, including 18,946 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 0.48 (18946 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.65-9014G>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.65-9014G>A		intron_variant		1	NM_002203.4	ENSP00000296585	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73429 AN: 151914 Hom.: 18942 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.483 AC: 73446 AN: 152032 Hom.: 18946 Cov.: 32 AF XY: 0.480 AC XY: 35678 AN XY: 74310

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.497

Alfa AF: 0.562 Hom.: 40837

Bravo AF: 0.472

Asia WGS AF: 0.311 AC: 1082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4865756; hg19: chr5-52313564; COSMIC: COSV56857765;