Genetic Variant ITGA2-AS1:n.189+843G>C (chr5-52989247-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000505701.5(ITGA2-AS1):n.189+843G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 585,680 control chromosomes in the GnomAD database, including 5,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1685 hom., cov: 32)

Exomes 𝑓: 0.12 ( 3684 hom. )

Consequence

ITGA2-AS1
ENST00000505701.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.489

Variant links:

Genes affected

ITGA2-AS1 (HGNC:40306): (ITGA2 antisense RNA 1)

ITGA2-AS1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-52989247-C-G is Benign according to our data. Variant chr5-52989247-C-G is described in ClinVar as [Benign]. Clinvar id is 1246532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4 link	c.-222C>G		upstream_gene_variant		ENST00000296585.10	NP_002194.2	P17301

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10 link	c.-222C>G		upstream_gene_variant		1	NM_002203.4	ENSP00000296585.5		P17301

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

21154

AN:

139908

Hom.:

1685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0998

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.0915

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.130

GnomAD4 exome

AF:

0.123

AC:

54991

AN:

445678

Hom.:

3684

AF XY:

0.126

AC XY:

29675

AN XY:

234720

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.0753

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.0941

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.151

AC:

21174

AN:

140002

Hom.:

1685

Cov.:

AF XY:

0.151

AC XY:

10277

AN XY:

67856

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0996

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0602

Hom.:

Bravo

AF:

0.143

Asia WGS

AF:

0.170

AC:

589

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 11313353) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.2

DANN

Benign

0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over