5-53042253-T-G

Variant names:

• chr5-53042253-T-G
• rs1363192
• NM_002203.4:c.295+32T>G

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.295+32T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,258,426 control chromosomes in the GnomAD database, including 51,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5803 hom., cov: 32)
  • Exomes 𝑓: 0.28 (46146 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0240
• Publications: 9 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=-0.8).
• BP6: Variant 5-53042253-T-G is Benign according to our data. Variant chr5-53042253-T-G is described in ClinVar as Benign. ClinVar VariationId is 1281085.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.295+32T>G		intron_variant	Intron 3 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.295+32T>G		intron_variant	Intron 3 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41728 AN: 151908 Hom.: 5802 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: 0.238

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.273

GnomAD2 exomes AF: 0.291 AC: 72895 AN: 250204 AF XY: 0.290

Gnomad AFR exome AF: 0.238

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: 0.285 AC: 315067 AN: 1106400 Hom.: 46146 Cov.: 15 AF XY: 0.285 AC XY: 161526 AN XY: 567128

African (AFR) AF: 0.235 AC: 6221 AN: 26516

American (AMR) AF: 0.353 AC: 15596 AN: 44204

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6203 AN: 23922

East Asian (EAS) AF: 0.278 AC: 10573 AN: 37984

South Asian (SAS) AF: 0.300 AC: 23720 AN: 79068

European-Finnish (FIN) AF: 0.329 AC: 17456 AN: 53094

Middle Eastern (MID) AF: 0.225 AC: 1139 AN: 5052

European-Non Finnish (NFE) AF: 0.280 AC: 220436 AN: 787768

Other (OTH) AF: 0.281 AC: 13723 AN: 48792

GnomAD4 genome AF: 0.275 AC: 41752 AN: 152026 Hom.: 5803 Cov.: 32 AF XY: 0.278 AC XY: 20660 AN XY: 74300

African (AFR) AF: 0.234 AC: 9713 AN: 41476

American (AMR) AF: 0.322 AC: 4910 AN: 15266

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

East Asian (EAS) AF: 0.238 AC: 1233 AN: 5172

South Asian (SAS) AF: 0.293 AC: 1416 AN: 4826

European-Finnish (FIN) AF: 0.330 AC: 3486 AN: 10566

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

European-Non Finnish (NFE) AF: 0.284 AC: 19292 AN: 67936

Other (OTH) AF: 0.274 AC: 579 AN: 2112

Alfa AF: 0.281 Hom.: 3320

Bravo AF: 0.273

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.75
PhyloP100		0.024
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: rs1363192; hg19: chr5-52338083; COSMIC: COSV56857563;