5-53070949-G-A

Variant names:

• chr5-53070949-G-A
• rs3212574
• NM_002203.4:c.2235+689G>A

Variant summary

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

The NM_002203.4(ITGA2):​c.2235+689G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,810 control chromosomes in the GnomAD database, including 2,657 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 0.18 (2657 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• Publications: 7 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 (NFE) allele frequency at 95% confidence interval = 0.212 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.2235+689G>A		intron	N/A	NP_002194.2
	ITGA2	NR_073103.2		n.2352+689G>A		intron	N/A
	ITGA2	NR_073104.2		n.2352+689G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.2235+689G>A		intron	N/A	ENSP00000296585.5
	ITGA2	ENST00000509814.5	TSL:1	n.2235+689G>A		intron	N/A	ENSP00000424397.1
	ITGA2	ENST00000509960.5	TSL:1	n.*350+689G>A		intron	N/A	ENSP00000424642.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27947 AN: 151692 Hom.: 2659 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.184 AC: 27943 AN: 151810 Hom.: 2657 Cov.: 32 AF XY: 0.183 AC XY: 13608 AN XY: 74178

African (AFR) AF: 0.154 AC: 6392 AN: 41458

American (AMR) AF: 0.143 AC: 2178 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 535 AN: 3460

East Asian (EAS) AF: 0.0563 AC: 289 AN: 5130

South Asian (SAS) AF: 0.199 AC: 958 AN: 4814

European-Finnish (FIN) AF: 0.227 AC: 2400 AN: 10556

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14608 AN: 67850

Other (OTH) AF: 0.179 AC: 377 AN: 2108

Alfa AF: 0.190 Hom.: 2195

Bravo AF: 0.176

Asia WGS AF: 0.129 AC: 448 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.42
PhyloP100		-0.76
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: rs3212574; hg19: chr5-52366779;