NM_002203.4:c.64+11880C>T

Variant names:

• chr5-53001412-C-T
• rs1645761
• NM_002203.4:c.64+11880C>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.64+11880C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,066 control chromosomes in the GnomAD database, including 49,502 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 0.80 (49502 hom., cov: 31)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.64+11880C>T		intron_variant	Intron 1 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.64+11880C>T		intron_variant	Intron 1 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.803 AC: 121993 AN: 151948 Hom.: 49475 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.803 AC: 122079 AN: 152066 Hom.: 49502 Cov.: 31 AF XY: 0.804 AC XY: 59747 AN XY: 74336

African (AFR) AF: 0.695 AC: 28813 AN: 41452

American (AMR) AF: 0.769 AC: 11751 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3024 AN: 3472

East Asian (EAS) AF: 0.663 AC: 3410 AN: 5144

South Asian (SAS) AF: 0.841 AC: 4059 AN: 4828

European-Finnish (FIN) AF: 0.863 AC: 9128 AN: 10574

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59069 AN: 67996

Other (OTH) AF: 0.810 AC: 1712 AN: 2114

Alfa AF: 0.853 Hom.: 80218

Bravo AF: 0.787

Asia WGS AF: 0.724 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.21
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: rs1645761; hg19: chr5-52297242;