rs6880055

Variant names:

• chr5-53093598-A-G
• rs6880055
• NM_002203.4:c.*2999A>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.*2999A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,062 control chromosomes in the GnomAD database, including 7,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7512 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ITGA2 NM_002203.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0820
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 5-53093598-A-G is Benign according to our data. Variant chr5-53093598-A-G is described in ClinVar as Benign. ClinVar VariationId is 353840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.348 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.*2999A>G		3_prime_UTR	Exon 30 of 30	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.6559A>G		non_coding_transcript_exon	Exon 29 of 29
	ITGA2	NR_073104.2		n.6520A>G		non_coding_transcript_exon	Exon 29 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.*2999A>G		3_prime_UTR	Exon 30 of 30	ENSP00000296585.5	P17301

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47212 AN: 151944 Hom.: 7510 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.312

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.311 AC: 47227 AN: 152062 Hom.: 7512 Cov.: 32 AF XY: 0.313 AC XY: 23275 AN XY: 74326

African (AFR) AF: 0.240 AC: 9942 AN: 41462

American (AMR) AF: 0.356 AC: 5441 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3470

East Asian (EAS) AF: 0.239 AC: 1236 AN: 5170

South Asian (SAS) AF: 0.316 AC: 1524 AN: 4824

European-Finnish (FIN) AF: 0.379 AC: 4009 AN: 10570

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23018 AN: 67982

Other (OTH) AF: 0.313 AC: 660 AN: 2110

Alfa AF: 0.337 Hom.: 1076

Bravo AF: 0.306

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Combined molybdoflavoprotein enzyme deficiency (1)
-	-	1	not provided (1)
-	-	1	Platelet-type bleeding disorder 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.3
DANN	Benign	0.81
PhyloP100		0.082
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: rs6880055; hg19: chr5-52389428;