rs2974987

chr5-53055412-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002203.4(ITGA2):c.780-126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 802,852 control chromosomes in the GnomAD database, including 92,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (17359 hom., cov: 32)
  • Exomes 𝑓: 0.48 (75315 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.267

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-53055412-A-G is Benign according to our data. Variant chr5-53055412-A-G is described in ClinVar as [Benign]. Clinvar id is 1251873.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA2	NM_002203.4	c.780-126A>G		intron_variant		ENST00000296585.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA2	ENST00000296585.10	c.780-126A>G		intron_variant		1	NM_002203.4	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72468 AN: 151788 Hom.: 17332 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.479 AC: 311953 AN: 650946 Hom.: 75315 AF XY: 0.479 AC XY: 165410 AN XY: 345386

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.403

Gnomad4 SAS exome AF: 0.463

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome AF: 0.478 AC: 72540 AN: 151906 Hom.: 17359 Cov.: 32 AF XY: 0.474 AC XY: 35171 AN XY: 74228

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.501

Alfa AF: 0.486 Hom.: 6879

Bravo AF: 0.483

Asia WGS AF: 0.423 AC: 1474 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	1.9
Dann	Benign	0.58

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: rs2974987; hg19: chr5-52351242; COSMIC: COSV56868242;