rs1991013

Variant names:

• chr5-53064104-A-G
• rs1991013
• NM_002203.4:c.1603-808A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002203.4(ITGA2):​c.1603-808A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,650 control chromosomes in the GnomAD database, including 17,686 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 (17686 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.1603-808A>G		intron_variant	Intron 13 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.1603-808A>G		intron_variant	Intron 13 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73112 AN: 151532 Hom.: 17664 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.483 AC: 73178 AN: 151650 Hom.: 17686 Cov.: 32 AF XY: 0.479 AC XY: 35457 AN XY: 74092

African (AFR) AF: 0.478 AC: 19781 AN: 41414

American (AMR) AF: 0.518 AC: 7876 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1669 AN: 3462

East Asian (EAS) AF: 0.333 AC: 1707 AN: 5124

South Asian (SAS) AF: 0.439 AC: 2117 AN: 4820

European-Finnish (FIN) AF: 0.459 AC: 4834 AN: 10532

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33558 AN: 67782

Other (OTH) AF: 0.507 AC: 1063 AN: 2098

Alfa AF: 0.494 Hom.: 2858

Bravo AF: 0.488

Asia WGS AF: 0.419 AC: 1450 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.38
PhyloP100		-0.73
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: rs1991013; hg19: chr5-52359934;