5-52989345-G-A

Position:

• chr5-52989345-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000662246.1(ITGA2-AS1):​n.75+745C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,004,716 control chromosomes in the GnomAD database, including 1,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (643 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (375 hom.)
• Consequence: ITGA2-AS1 ENST00000662246.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.21

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-52989345-G-A is Benign according to our data. Variant chr5-52989345-G-A is described in ClinVar as [Benign]. Clinvar id is 353728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA2	NM_002203.4			upstream_gene_variant		ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA2-AS1	ENST00000662246.1	n.75+745C>T		intron_variant, non_coding_transcript_variant
ITGA2	ENST00000296585.10			upstream_gene_variant		1	NM_002203.4	ENSP00000296585	P1

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7526 AN: 152212 Hom.: 642 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.00576 AC: 4908 AN: 852388 Hom.: 375 Cov.: 12 AF XY: 0.00488 AC XY: 2162 AN XY: 443292

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.00866

Gnomad4 ASJ exome AF: 0.000138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000425

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000310

Gnomad4 OTH exome AF: 0.0124

GnomAD4 genome AF: 0.0495 AC: 7533 AN: 152328 Hom.: 643 Cov.: 33 AF XY: 0.0467 AC XY: 3480 AN XY: 74490

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0248 Hom.: 49

Bravo AF: 0.0565

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Platelet-type bleeding disorder 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs3212385; hg19: chr5-52285175;