5-53076044-C-T

Variant names:

• chr5-53076044-C-T
• rs10513009
• NM_002203.4:c.2825+740C>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.2825+740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,962 control chromosomes in the GnomAD database, including 1,149 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 0.11 (1149 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.2825+740C>T		intron_variant	Intron 23 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.2825+740C>T		intron_variant	Intron 23 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16896 AN: 151844 Hom.: 1142 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0897

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.111 AC: 16941 AN: 151962 Hom.: 1149 Cov.: 32 AF XY: 0.107 AC XY: 7972 AN XY: 74260

African (AFR) AF: 0.186 AC: 7693 AN: 41464

American (AMR) AF: 0.0844 AC: 1287 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3470

East Asian (EAS) AF: 0.0265 AC: 136 AN: 5124

South Asian (SAS) AF: 0.0870 AC: 420 AN: 4826

European-Finnish (FIN) AF: 0.0547 AC: 580 AN: 10606

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0897 AC: 6093 AN: 67912

Other (OTH) AF: 0.123 AC: 259 AN: 2106

Alfa AF: 0.0800 Hom.: 295

Bravo AF: 0.117

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.35
PhyloP100		-0.81
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: rs10513009; hg19: chr5-52371874;