rs1126643

Variant names:

• chr5-53051539-C-T
• rs1126643
• NM_002203.4:c.759C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-53051539-C-T
• chr5-53051539-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BA1

The NM_002203.4(ITGA2):​c.759C>T​(p.Phe253Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,611,596 control chromosomes in the GnomAD database, including 124,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10259 hom., cov: 31)
  • Exomes 𝑓: 0.39 (114694 hom.)
• Consequence: ITGA2 NM_002203.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.61
• Publications: 161 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BP6: Variant 5-53051539-C-T is Benign according to our data. Variant chr5-53051539-C-T is described in ClinVar as Benign. ClinVar VariationId is 353741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 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.759C>T	p.Phe253Phe	synonymous	Exon 7 of 30	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.876C>T		non_coding_transcript_exon	Exon 7 of 29
	ITGA2	NR_073104.2		n.876C>T		non_coding_transcript_exon	Exon 7 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.759C>T	p.Phe253Phe	synonymous	Exon 7 of 30	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.759C>T		non_coding_transcript_exon	Exon 7 of 29	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.759C>T		non_coding_transcript_exon	Exon 7 of 30	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55405 AN: 151598 Hom.: 10260 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.374

GnomAD2 exomes AF: 0.386 AC: 96856 AN: 250968 AF XY: 0.385

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.396

Gnomad NFE exome AF: 0.397

Gnomad OTH exome AF: 0.384

GnomAD4 exome AF: 0.394 AC: 575320 AN: 1459880 Hom.: 114694 Cov.: 39 AF XY: 0.393 AC XY: 285560 AN XY: 726314

African (AFR) AF: 0.289 AC: 9651 AN: 33414

American (AMR) AF: 0.453 AC: 20237 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9917 AN: 26098

East Asian (EAS) AF: 0.358 AC: 14200 AN: 39616

South Asian (SAS) AF: 0.365 AC: 31482 AN: 86218

European-Finnish (FIN) AF: 0.396 AC: 21176 AN: 53414

Middle Eastern (MID) AF: 0.371 AC: 2139 AN: 5758

European-Non Finnish (NFE) AF: 0.399 AC: 443149 AN: 1110344

Other (OTH) AF: 0.387 AC: 23369 AN: 60314

GnomAD4 genome AF: 0.365 AC: 55426 AN: 151716 Hom.: 10259 Cov.: 31 AF XY: 0.366 AC XY: 27111 AN XY: 74128

African (AFR) AF: 0.290 AC: 11990 AN: 41358

American (AMR) AF: 0.428 AC: 6515 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1572 AN: 5150

South Asian (SAS) AF: 0.352 AC: 1687 AN: 4794

European-Finnish (FIN) AF: 0.396 AC: 4166 AN: 10508

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

European-Non Finnish (NFE) AF: 0.397 AC: 26955 AN: 67898

Other (OTH) AF: 0.375 AC: 788 AN: 2104

Alfa AF: 0.387 Hom.: 41618

Bravo AF: 0.366

Asia WGS AF: 0.335 AC: 1165 AN: 3476

EpiCase AF: 0.393

EpiControl AF: 0.386

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	-0.15
CADD	Benign	7.8
DANN	Benign	0.82
PhyloP100		1.6
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: rs1126643; hg19: chr5-52347369; COSMIC: COSV56856401;