5-53048780-A-G

Variant names:

• chr5-53048780-A-G
• rs1421933
• NM_002203.4:c.630+10A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

ITGA2 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 9

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 353737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002203.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	NM_002203.4	MANE Select	c.630+10A>G		intron	N/A	NP_002194.2
	ITGA2	NR_073103.2		n.747+10A>G		intron	N/A
	ITGA2	NR_073104.2		n.747+10A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.630+10A>G		intron	N/A	ENSP00000296585.5
	ITGA2	ENST00000509814.5	TSL:1	n.630+10A>G		intron	N/A	ENSP00000424397.1
	ITGA2	ENST00000509960.5	TSL:1	n.630+10A>G		intron	N/A	ENSP00000424642.1

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

GnomAD2 exomes AF: 0.719 AC: 179960 AN: 250378 AF XY: 0.720

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 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

African (AFR) AF: 0.793 AC: 26516 AN: 33446

American (AMR) AF: 0.726 AC: 32472 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 19323 AN: 26118

East Asian (EAS) AF: 0.593 AC: 23511 AN: 39658

South Asian (SAS) AF: 0.742 AC: 63991 AN: 86184

European-Finnish (FIN) AF: 0.731 AC: 39027 AN: 53382

Middle Eastern (MID) AF: 0.711 AC: 4095 AN: 5756

European-Non Finnish (NFE) AF: 0.728 AC: 808967 AN: 1110584

Other (OTH) AF: 0.724 AC: 43672 AN: 60346

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

African (AFR) AF: 0.785 AC: 32555 AN: 41484

American (AMR) AF: 0.761 AC: 11619 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2535 AN: 3472

East Asian (EAS) AF: 0.528 AC: 2726 AN: 5164

South Asian (SAS) AF: 0.725 AC: 3495 AN: 4824

European-Finnish (FIN) AF: 0.732 AC: 7752 AN: 10588

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49808 AN: 68002

Other (OTH) AF: 0.750 AC: 1585 AN: 2112

Alfa AF: 0.732 Hom.: 24001

Bravo AF: 0.743

Asia WGS AF: 0.654 AC: 2276 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Platelet-type bleeding disorder 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1421933; hg19: chr5-52344610;