rs2287871

chr5-53071876-T-Cchr5-53071876-T-G

Variant summary

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

The NM_002203.4(ITGA2):c.2236-62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,152,200 control chromosomes in the GnomAD database, including 134,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17322 hom., cov: 32)
  • Exomes 𝑓: 0.48 (117323 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.478

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-53071876-T-C is Benign according to our data. Variant chr5-53071876-T-C is described in ClinVar as [Benign]. Clinvar id is 802121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA2	NM_002203.4	c.2236-62T>C		intron_variant		ENST00000296585.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA2	ENST00000296585.10	c.2236-62T>C		intron_variant		1	NM_002203.4	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72365 AN: 151648 Hom.: 17302 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.483 AC: 482889 AN: 1000434 Hom.: 117323 AF XY: 0.482 AC XY: 249084 AN XY: 516902

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.497

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome AF: 0.477 AC: 72428 AN: 151766 Hom.: 17322 Cov.: 32 AF XY: 0.474 AC XY: 35156 AN XY: 74168

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.497

Alfa AF: 0.482 Hom.: 27651

Bravo AF: 0.484

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Platelet-type bleeding disorder 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.2
Dann	Benign	0.70

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: rs2287871; hg19: chr5-52367706; COSMIC: COSV56857596;