5-52989287-T-C

Variant names:

• chr5-52989287-T-C
• rs28095
• ENST00000503559.1:n.189+803A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000503559.1(ITGA2-AS1):​n.189+803A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 671,630 control chromosomes in the GnomAD database, including 138,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (29208 hom., cov: 27)
  • Exomes 𝑓: 0.64 (109543 hom.)
• Consequence: ITGA2-AS1 ENST00000503559.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0430
• Publications: 14 publications found

Genes affected

ITGA2-AS1 (HGNC:40306): (ITGA2 antisense RNA 1)

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 5-52989287-T-C is Benign according to our data. Variant chr5-52989287-T-C is described in ClinVar as Benign. ClinVar VariationId is 1237373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.-182T>C		upstream_gene_variant		ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.-182T>C		upstream_gene_variant		1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.646 AC: 93436 AN: 144596 Hom.: 29170 Cov.: 27

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.642 AC: 338329 AN: 526932 Hom.: 109543 Cov.: 5 AF XY: 0.648 AC XY: 180485 AN XY: 278470

African (AFR) AF: 0.568 AC: 8566 AN: 15070

American (AMR) AF: 0.575 AC: 18420 AN: 32020

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 9560 AN: 16896

East Asian (EAS) AF: 0.534 AC: 16657 AN: 31172

South Asian (SAS) AF: 0.735 AC: 40542 AN: 55150

European-Finnish (FIN) AF: 0.630 AC: 26949 AN: 42810

Middle Eastern (MID) AF: 0.550 AC: 1422 AN: 2586

European-Non Finnish (NFE) AF: 0.655 AC: 198325 AN: 302572

Other (OTH) AF: 0.624 AC: 17888 AN: 28656

GnomAD4 genome AF: 0.646 AC: 93522 AN: 144698 Hom.: 29208 Cov.: 27 AF XY: 0.648 AC XY: 45782 AN XY: 70702

African (AFR) AF: 0.594 AC: 23352 AN: 39290

American (AMR) AF: 0.623 AC: 9163 AN: 14700

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 1984 AN: 3308

East Asian (EAS) AF: 0.590 AC: 2768 AN: 4690

South Asian (SAS) AF: 0.750 AC: 3477 AN: 4634

European-Finnish (FIN) AF: 0.673 AC: 6454 AN: 9588

Middle Eastern (MID) AF: 0.599 AC: 164 AN: 274

European-Non Finnish (NFE) AF: 0.678 AC: 44308 AN: 65332

Other (OTH) AF: 0.628 AC: 1267 AN: 2016

Alfa AF: 0.548 Hom.: 1876

Bravo AF: 0.611

Asia WGS AF: 0.609 AC: 2110 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26202972, 11313353) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		-0.043
PromoterAI		0.18	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28095; hg19: chr5-52285117; COSMIC: COSV56859339;