5-53013185-C-T

Variant names:

• chr5-53013185-C-T
• rs152088
• NM_002203.4:c.65-13563C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002203.4(ITGA2):​c.65-13563C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,862 control chromosomes in the GnomAD database, including 3,863 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 0.22 (3863 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 9

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.65-13563C>T		intron_variant	Intron 1 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.65-13563C>T		intron_variant	Intron 1 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32812 AN: 151744 Hom.: 3859 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.216 AC: 32849 AN: 151862 Hom.: 3863 Cov.: 32 AF XY: 0.219 AC XY: 16291 AN XY: 74228

African (AFR) AF: 0.274 AC: 11330 AN: 41408

American (AMR) AF: 0.249 AC: 3786 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3464

East Asian (EAS) AF: 0.384 AC: 1982 AN: 5158

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4820

European-Finnish (FIN) AF: 0.163 AC: 1725 AN: 10556

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11445 AN: 67908

Other (OTH) AF: 0.196 AC: 414 AN: 2108

Alfa AF: 0.176 Hom.: 4140

Bravo AF: 0.226

Asia WGS AF: 0.361 AC: 1256 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	4.9
DANN	Benign	0.46
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs152088; hg19: chr5-52309015;