rs2303122

Variant names:

• chr5-53083447-C-T
• rs2303122
• NM_002203.4:c.3252C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-53083447-C-T
• chr5-53083447-C-G

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.3252C>T​(p.Phe1084Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,565,140 control chromosomes in the GnomAD database, including 104,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9326 hom., cov: 32)
  • Exomes 𝑓: 0.36 (95057 hom.)
• Consequence: ITGA2 NM_002203.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0620
• Publications: 27 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=-0.39).
• BP6: Variant 5-53083447-C-T is Benign according to our data. Variant chr5-53083447-C-T is described in ClinVar as Benign. ClinVar VariationId is 353779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.062 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.404 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.3252C>T	p.Phe1084Phe	synonymous	Exon 27 of 30	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.3266C>T		non_coding_transcript_exon	Exon 26 of 29
	ITGA2	NR_073104.2		n.3227C>T		non_coding_transcript_exon	Exon 26 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.3252C>T	p.Phe1084Phe	synonymous	Exon 27 of 30	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.*662C>T		non_coding_transcript_exon	Exon 26 of 29	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.*1367C>T		non_coding_transcript_exon	Exon 27 of 30	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52932 AN: 151844 Hom.: 9322 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.356

GnomAD2 exomes AF: 0.368 AC: 92207 AN: 250718 AF XY: 0.367

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.309

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.365 AC: 515459 AN: 1413180 Hom.: 95057 Cov.: 26 AF XY: 0.365 AC XY: 257491 AN XY: 706164

African (AFR) AF: 0.285 AC: 9292 AN: 32554

American (AMR) AF: 0.440 AC: 19636 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 9133 AN: 25830

East Asian (EAS) AF: 0.365 AC: 14392 AN: 39406

South Asian (SAS) AF: 0.357 AC: 30440 AN: 85254

European-Finnish (FIN) AF: 0.392 AC: 20916 AN: 53342

Middle Eastern (MID) AF: 0.339 AC: 1916 AN: 5656

European-Non Finnish (NFE) AF: 0.364 AC: 388505 AN: 1067730

Other (OTH) AF: 0.361 AC: 21229 AN: 58782

GnomAD4 genome AF: 0.348 AC: 52951 AN: 151960 Hom.: 9326 Cov.: 32 AF XY: 0.351 AC XY: 26052 AN XY: 74246

African (AFR) AF: 0.285 AC: 11825 AN: 41432

American (AMR) AF: 0.412 AC: 6289 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1620 AN: 5166

South Asian (SAS) AF: 0.347 AC: 1672 AN: 4820

European-Finnish (FIN) AF: 0.395 AC: 4171 AN: 10552

Middle Eastern (MID) AF: 0.334 AC: 97 AN: 290

European-Non Finnish (NFE) AF: 0.368 AC: 24971 AN: 67944

Other (OTH) AF: 0.356 AC: 752 AN: 2112

Alfa AF: 0.359 Hom.: 35044

Bravo AF: 0.348

Asia WGS AF: 0.334 AC: 1162 AN: 3478

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	-0.39
CADD	Benign	0.81
DANN	Benign	0.50
PhyloP100		0.062
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs2303122; hg19: chr5-52379277; COSMIC: COSV56857327;