rs3212441

Variant names:

• chr5-53042078-C-T
• rs3212441
• NM_002203.4:c.186-34C>T

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.186-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,215,734 control chromosomes in the GnomAD database, including 49,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5809 hom., cov: 32)
  • Exomes 𝑓: 0.28 (43863 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.89
• Publications: 7 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=-0.87).
• BP6: Variant 5-53042078-C-T is Benign according to our data. Variant chr5-53042078-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 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.186-34C>T		intron	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.303-34C>T		intron	N/A
	ITGA2	NR_073104.2		n.303-34C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.186-34C>T		intron	N/A	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.186-34C>T		intron	N/A	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.186-34C>T		intron	N/A	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41737 AN: 151880 Hom.: 5808 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.272

GnomAD2 exomes AF: 0.291 AC: 72927 AN: 250482 AF XY: 0.290

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.230

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.284 AC: 301589 AN: 1063738 Hom.: 43863 Cov.: 14 AF XY: 0.284 AC XY: 155329 AN XY: 547802

African (AFR) AF: 0.234 AC: 5985 AN: 25614

American (AMR) AF: 0.353 AC: 15580 AN: 44160

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6125 AN: 23672

East Asian (EAS) AF: 0.278 AC: 10533 AN: 37826

South Asian (SAS) AF: 0.299 AC: 23397 AN: 78364

European-Finnish (FIN) AF: 0.328 AC: 17455 AN: 53136

Middle Eastern (MID) AF: 0.225 AC: 1140 AN: 5058

European-Non Finnish (NFE) AF: 0.278 AC: 208043 AN: 748600

Other (OTH) AF: 0.282 AC: 13331 AN: 47308

GnomAD4 genome AF: 0.275 AC: 41760 AN: 151996 Hom.: 5809 Cov.: 32 AF XY: 0.278 AC XY: 20653 AN XY: 74266

African (AFR) AF: 0.234 AC: 9711 AN: 41484

American (AMR) AF: 0.322 AC: 4912 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1237 AN: 5170

South Asian (SAS) AF: 0.293 AC: 1414 AN: 4820

European-Finnish (FIN) AF: 0.331 AC: 3484 AN: 10536

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19303 AN: 67932

Other (OTH) AF: 0.273 AC: 576 AN: 2110

Alfa AF: 0.281 Hom.: 1386

Bravo AF: 0.273

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.53
PhyloP100		-1.9
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3212441;

hg19: chr5-52337908;

COSMIC: COSV56857556;