5-53048780-A-G

Variant names:

• chr5-53048780-A-G
• rs1421933
• NM_002203.4:c.630+10A>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.630+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,612,300 control chromosomes in the GnomAD database, including 429,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42162 hom., cov: 32)
  • Exomes 𝑓: 0.73 (387068 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.162

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=-0.82).
• BP6: Variant 5-53048780-A-G is Benign according to our data. Variant chr5-53048780-A-G is described in ClinVar as [Benign]. Clinvar id is 353737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-53048780-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.630+10A>G		intron_variant	Intron 6 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.630+10A>G		intron_variant	Intron 6 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112822 AN: 151998 Hom.: 42105 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.751

GnomAD3 exomes AF: 0.719 AC: 179960 AN: 250378 Hom.: 65334 AF XY: 0.720 AC XY: 97505 AN XY: 135440

Gnomad AFR exome AF: 0.787

Gnomad AMR exome AF: 0.722

Gnomad ASJ exome AF: 0.738

Gnomad EAS exome AF: 0.517

Gnomad SAS exome AF: 0.741

Gnomad FIN exome AF: 0.738

Gnomad NFE exome AF: 0.730

Gnomad OTH exome AF: 0.713

GnomAD4 exome AF: 0.727 AC: 1061574 AN: 1460184 Hom.: 387068 Cov.: 42 AF XY: 0.728 AC XY: 528554 AN XY: 726428

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.740

Gnomad4 EAS exome AF: 0.593

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.731

Gnomad4 NFE exome AF: 0.728

Gnomad4 OTH exome AF: 0.724

GnomAD4 genome AF: 0.742 AC: 112937 AN: 152116 Hom.: 42162 Cov.: 32 AF XY: 0.741 AC XY: 55078 AN XY: 74358

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.750

Alfa AF: 0.733 Hom.: 21983

Bravo AF: 0.743

Asia WGS AF: 0.654 AC: 2276 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Platelet-type bleeding disorder 9 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.1
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1421933; hg19: chr5-52344610;