5-53047731-A-G

Variant names:

• chr5-53047731-A-G
• rs3212478
• NM_002203.4:c.388-632A>G

Variant summary

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

The NM_002203.4(ITGA2):​c.388-632A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,080 control chromosomes in the GnomAD database, including 5,820 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 0.27 (5820 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• 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=-0.96).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	NM_002203.4	MANE Select	c.388-632A>G		intron	N/A	NP_002194.2
	ITGA2	NR_073103.2		n.505-632A>G		intron	N/A
	ITGA2	NR_073104.2		n.505-632A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.388-632A>G		intron	N/A	ENSP00000296585.5
	ITGA2	ENST00000509814.5	TSL:1	n.388-632A>G		intron	N/A	ENSP00000424397.1
	ITGA2	ENST00000509960.5	TSL:1	n.388-632A>G		intron	N/A	ENSP00000424642.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41747 AN: 151962 Hom.: 5819 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.217

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: 0.275 AC: 41770 AN: 152080 Hom.: 5820 Cov.: 32 AF XY: 0.278 AC XY: 20654 AN XY: 74320

African (AFR) AF: 0.235 AC: 9736 AN: 41518

American (AMR) AF: 0.321 AC: 4901 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 848 AN: 3460

East Asian (EAS) AF: 0.240 AC: 1238 AN: 5162

South Asian (SAS) AF: 0.293 AC: 1413 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3483 AN: 10564

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19300 AN: 67970

Other (OTH) AF: 0.274 AC: 579 AN: 2114

Alfa AF: 0.205 Hom.: 557

Bravo AF: 0.273

Asia WGS AF: 0.293 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.035
DANN	Benign	0.47
PhyloP100		-2.6
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: rs3212478; hg19: chr5-52343561;