chr5-53055412-A-G

Variant names:

• chr5-53055412-A-G
• rs2974987
• NM_002203.4:c.780-126A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	NM_002203.4	MANE Select	c.780-126A>G		intron	N/A	NP_002194.2
	ITGA2	NR_073103.2		n.897-126A>G		intron	N/A
	ITGA2	NR_073104.2		n.897-126A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.780-126A>G		intron	N/A	ENSP00000296585.5
	ITGA2	ENST00000509814.5	TSL:1	n.780-126A>G		intron	N/A	ENSP00000424397.1
	ITGA2	ENST00000509960.5	TSL:1	n.780-126A>G		intron	N/A	ENSP00000424642.1

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

African (AFR) AF: 0.483 AC: 8007 AN: 16580

American (AMR) AF: 0.514 AC: 16415 AN: 31932

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 9595 AN: 19366

East Asian (EAS) AF: 0.403 AC: 13126 AN: 32546

South Asian (SAS) AF: 0.463 AC: 28486 AN: 61492

European-Finnish (FIN) AF: 0.450 AC: 16461 AN: 36564

Middle Eastern (MID) AF: 0.524 AC: 1445 AN: 2758

European-Non Finnish (NFE) AF: 0.486 AC: 202356 AN: 416562

Other (OTH) AF: 0.485 AC: 16062 AN: 33146

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

African (AFR) AF: 0.476 AC: 19736 AN: 41432

American (AMR) AF: 0.507 AC: 7733 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1652 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1707 AN: 5144

South Asian (SAS) AF: 0.446 AC: 2150 AN: 4824

European-Finnish (FIN) AF: 0.450 AC: 4754 AN: 10570

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33187 AN: 67926

Other (OTH) AF: 0.501 AC: 1054 AN: 2104

Alfa AF: 0.486 Hom.: 7242

Bravo AF: 0.483

Asia WGS AF: 0.423 AC: 1474 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.58
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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