rs3756541

Variant names:

• chr5-53007515-G-A
• rs3756541
• NM_002203.4:c.64+17983G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-53007515-G-A
• chr5-53007515-G-T

Variant summary

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

The ENST00000296585.10(ITGA2):​c.64+17983G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 146,930 control chromosomes in the GnomAD database, including 5,407 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 0.25 (5407 hom., cov: 30)
• Consequence: ITGA2 ENST00000296585.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000296585.10. 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.64+17983G>A		intron	N/A	NP_002194.2
	ITGA2	NR_073103.2		n.181+17983G>A		intron	N/A
	ITGA2	NR_073104.2		n.181+17983G>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.64+17983G>A		intron	N/A	ENSP00000296585.5
	ITGA2	ENST00000509814.5	TSL:1	n.64+17983G>A		intron	N/A	ENSP00000424397.1
	ITGA2	ENST00000509960.5	TSL:1	n.64+17983G>A		intron	N/A	ENSP00000424642.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 37079 AN: 146842 Hom.: 5406 Cov.: 30

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.289

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.252 AC: 37086 AN: 146930 Hom.: 5407 Cov.: 30 AF XY: 0.254 AC XY: 18197 AN XY: 71508

African (AFR) AF: 0.0862 AC: 3412 AN: 39596

American (AMR) AF: 0.278 AC: 4112 AN: 14786

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 966 AN: 3396

East Asian (EAS) AF: 0.172 AC: 874 AN: 5068

South Asian (SAS) AF: 0.326 AC: 1518 AN: 4662

European-Finnish (FIN) AF: 0.331 AC: 3160 AN: 9552

Middle Eastern (MID) AF: 0.284 AC: 80 AN: 282

European-Non Finnish (NFE) AF: 0.333 AC: 22177 AN: 66644

Other (OTH) AF: 0.259 AC: 530 AN: 2050

Alfa AF: 0.00450 Hom.: 11

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.72
DANN	Benign	0.53
PhyloP100		0.23
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: rs3756541; hg19: chr5-52303345;