rs3212418

Variant names:

• chr5-53020342-C-T
• rs3212418
• NM_002203.4:c.65-6406C>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.65-6406C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,944 control chromosomes in the GnomAD database, including 18,972 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 0.48 (18972 hom., cov: 31)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.65-6406C>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.65-6406C>T		intron_variant	Intron 1 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73524 AN: 151826 Hom.: 18967 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.484 AC: 73543 AN: 151944 Hom.: 18972 Cov.: 31 AF XY: 0.481 AC XY: 35717 AN XY: 74264

African (AFR) AF: 0.321 AC: 13323 AN: 41442

American (AMR) AF: 0.511 AC: 7803 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2129 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1302 AN: 5146

South Asian (SAS) AF: 0.424 AC: 2045 AN: 4818

European-Finnish (FIN) AF: 0.554 AC: 5825 AN: 10518

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39335 AN: 67962

Other (OTH) AF: 0.499 AC: 1053 AN: 2112

Alfa AF: 0.539 Hom.: 12032

Bravo AF: 0.473

Asia WGS AF: 0.310 AC: 1076 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-0.25
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: rs3212418; hg19: chr5-52316172; COSMIC: COSV56857772;