chr5-53044844-C-T

Variant names:

• chr5-53044844-C-T
• rs3212460
• NM_002203.4:c.296-157C>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.296-157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 152,302 control chromosomes in the GnomAD database, including 159 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 0.039 (159 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0681 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.296-157C>T		intron	N/A	NP_002194.2
	ITGA2	NR_073103.2		n.413-157C>T		intron	N/A
	ITGA2	NR_073104.2		n.413-157C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.296-157C>T		intron	N/A	ENSP00000296585.5
	ITGA2	ENST00000509814.5	TSL:1	n.296-157C>T		intron	N/A	ENSP00000424397.1
	ITGA2	ENST00000509960.5	TSL:1	n.296-157C>T		intron	N/A	ENSP00000424642.1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5921 AN: 152184 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0439

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

GnomAD4 genome AF: 0.0389 AC: 5928 AN: 152302 Hom.: 159 Cov.: 32 AF XY: 0.0389 AC XY: 2899 AN XY: 74460

African (AFR) AF: 0.0365 AC: 1517 AN: 41550

American (AMR) AF: 0.0596 AC: 912 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3470

East Asian (EAS) AF: 0.0742 AC: 385 AN: 5186

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4828

European-Finnish (FIN) AF: 0.0206 AC: 219 AN: 10610

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0352 AC: 2395 AN: 68038

Other (OTH) AF: 0.0440 AC: 93 AN: 2116

Alfa AF: 0.0185 Hom.: 12

Bravo AF: 0.0426

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.77
PhyloP100		0.27
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: rs3212460; hg19: chr5-52340674;