NM_002203.4:c.2083+412C>T

Variant names:

• chr5-53067669-C-T
• rs2056403
• NM_002203.4:c.2083+412C>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.2083+412C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 151,780 control chromosomes in the GnomAD database, including 42,259 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 0.74 (42259 hom., cov: 33)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.2083+412C>T		intron_variant	Intron 16 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.2083+412C>T		intron_variant	Intron 16 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112875 AN: 151662 Hom.: 42202 Cov.: 33

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.744 AC: 112990 AN: 151780 Hom.: 42259 Cov.: 33 AF XY: 0.743 AC XY: 55102 AN XY: 74150

African (AFR) AF: 0.786 AC: 32574 AN: 41468

American (AMR) AF: 0.766 AC: 11667 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2673 AN: 3470

East Asian (EAS) AF: 0.527 AC: 2696 AN: 5112

South Asian (SAS) AF: 0.718 AC: 3460 AN: 4820

European-Finnish (FIN) AF: 0.735 AC: 7768 AN: 10566

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49699 AN: 67806

Other (OTH) AF: 0.756 AC: 1590 AN: 2104

Alfa AF: 0.674 Hom.: 2165

Bravo AF: 0.745

Asia WGS AF: 0.651 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.081
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: rs2056403; hg19: chr5-52363499;