rs2056402

Variant names:

• chr5-53067796-A-T
• rs2056402
• NM_002203.4:c.2083+539A>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.2083+539A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 152,000 control chromosomes in the GnomAD database, including 454 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 0.064 (454 hom., cov: 33)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.2083+539A>T		intron_variant	Intron 16 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.2083+539A>T		intron_variant	Intron 16 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9757 AN: 151882 Hom.: 452 Cov.: 33

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0643 AC: 9767 AN: 152000 Hom.: 454 Cov.: 33 AF XY: 0.0663 AC XY: 4923 AN XY: 74304

African (AFR) AF: 0.0156 AC: 648 AN: 41538

American (AMR) AF: 0.121 AC: 1846 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3466

East Asian (EAS) AF: 0.161 AC: 827 AN: 5130

South Asian (SAS) AF: 0.0936 AC: 451 AN: 4818

European-Finnish (FIN) AF: 0.0843 AC: 895 AN: 10616

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4570 AN: 67866

Other (OTH) AF: 0.0700 AC: 148 AN: 2114

Alfa AF: 0.0621 Hom.: 46

Bravo AF: 0.0641

Asia WGS AF: 0.120 AC: 419 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	1.5
DANN	Benign	0.44
PhyloP100		0.37
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: rs2056402; hg19: chr5-52363626;