rs3212438

Variant names:

• chr5-53041926-A-G
• rs3212438
• NM_002203.4:c.186-186A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002203.4(ITGA2):​c.186-186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,000 control chromosomes in the GnomAD database, including 5,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (5783 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.876
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-53041926-A-G is Benign according to our data. Variant chr5-53041926-A-G is described in ClinVar as Benign. ClinVar VariationId is 1266358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002203.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	NM_002203.4	MANE Select	c.186-186A>G		intron	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.303-186A>G		intron	N/A
	ITGA2	NR_073104.2		n.303-186A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.186-186A>G		intron	N/A	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.186-186A>G		intron	N/A	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.186-186A>G		intron	N/A	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41670 AN: 151880 Hom.: 5782 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.274 AC: 41693 AN: 152000 Hom.: 5783 Cov.: 32 AF XY: 0.278 AC XY: 20621 AN XY: 74292

African (AFR) AF: 0.234 AC: 9703 AN: 41496

American (AMR) AF: 0.321 AC: 4895 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3466

East Asian (EAS) AF: 0.239 AC: 1237 AN: 5174

South Asian (SAS) AF: 0.293 AC: 1415 AN: 4826

European-Finnish (FIN) AF: 0.329 AC: 3478 AN: 10562

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19265 AN: 67908

Other (OTH) AF: 0.274 AC: 577 AN: 2108

Alfa AF: 0.287 Hom.: 985

Bravo AF: 0.273

Asia WGS AF: 0.292 AC: 1015 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.40
PhyloP100		-0.88
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: rs3212438; hg19: chr5-52337756;