rs1062535

Variant names:

• chr5-53055583-G-A
• rs1062535
• NM_002203.4:c.825G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-53055583-G-A
• chr5-53055583-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002203.4(ITGA2):​c.825G>A​(p.Thr275Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,612,484 control chromosomes in the GnomAD database, including 126,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10606 hom., cov: 32)
  • Exomes 𝑓: 0.40 (115853 hom.)
• Consequence: ITGA2 NM_002203.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.427
• Publications: 54 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 5-53055583-G-A is Benign according to our data. Variant chr5-53055583-G-A is described in ClinVar as Benign. ClinVar VariationId is 353744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.427 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.42 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.825G>A	p.Thr275Thr	synonymous	Exon 8 of 30	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.942G>A		non_coding_transcript_exon	Exon 8 of 29
	ITGA2	NR_073104.2		n.942G>A		non_coding_transcript_exon	Exon 8 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.825G>A	p.Thr275Thr	synonymous	Exon 8 of 30	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.825G>A		non_coding_transcript_exon	Exon 8 of 29	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.825G>A		non_coding_transcript_exon	Exon 8 of 30	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56486 AN: 151744 Hom.: 10601 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.381

GnomAD2 exomes AF: 0.388 AC: 97173 AN: 250348 AF XY: 0.387

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.397

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.396 AC: 578730 AN: 1460620 Hom.: 115853 Cov.: 38 AF XY: 0.395 AC XY: 287134 AN XY: 726640

African (AFR) AF: 0.310 AC: 10353 AN: 33410

American (AMR) AF: 0.454 AC: 20270 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9924 AN: 26096

East Asian (EAS) AF: 0.358 AC: 14211 AN: 39652

South Asian (SAS) AF: 0.365 AC: 31509 AN: 86240

European-Finnish (FIN) AF: 0.397 AC: 21192 AN: 53384

Middle Eastern (MID) AF: 0.372 AC: 2141 AN: 5758

European-Non Finnish (NFE) AF: 0.401 AC: 445611 AN: 1111082

Other (OTH) AF: 0.390 AC: 23519 AN: 60334

GnomAD4 genome AF: 0.372 AC: 56517 AN: 151864 Hom.: 10606 Cov.: 32 AF XY: 0.372 AC XY: 27626 AN XY: 74184

African (AFR) AF: 0.311 AC: 12899 AN: 41438

American (AMR) AF: 0.429 AC: 6534 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1567 AN: 5138

South Asian (SAS) AF: 0.351 AC: 1688 AN: 4812

European-Finnish (FIN) AF: 0.396 AC: 4177 AN: 10552

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27092 AN: 67910

Other (OTH) AF: 0.382 AC: 806 AN: 2112

Alfa AF: 0.387 Hom.: 35742

Bravo AF: 0.374

Asia WGS AF: 0.336 AC: 1169 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.387

ClinVar

ClinVar submissions

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	-0.40
CADD	Benign	7.2
DANN	Benign	0.60
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1062535; hg19: chr5-52351413; COSMIC: COSV56857578;