5-52989268-G-T

Variant names:

• chr5-52989268-G-T
• rs41308844
• ENST00000503559.1:n.189+822C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000505701.5(ITGA2-AS1):​n.189+822C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 650,998 control chromosomes in the GnomAD database, including 1,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (375 hom., cov: 32)
  • Exomes 𝑓: 0.070 (1546 hom.)
• Consequence: ITGA2-AS1 ENST00000505701.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.27
• Publications: 3 publications found

Genes affected

ITGA2-AS1 (HGNC:40306): (ITGA2 antisense RNA 1)

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=-0.89).
• BP6: Variant 5-52989268-G-T is Benign according to our data. Variant chr5-52989268-G-T is described in ClinVar as Benign. ClinVar VariationId is 1249583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000505701.5. 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-AS1	NR_186583.1		n.197+822C>A		intron	N/A
	ITGA2	NM_002203.4	MANE Select	c.-201G>T		upstream_gene	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.-84G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2-AS1	ENST00000503559.1	TSL:5	n.189+822C>A		intron	N/A
	ITGA2-AS1	ENST00000505701.5	TSL:4	n.189+822C>A		intron	N/A
	ITGA2-AS1	ENST00000662246.1		n.75+822C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9019 AN: 151620 Hom.: 374 Cov.: 32

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0664

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.0650

GnomAD4 exome AF: 0.0696 AC: 34744 AN: 499266 Hom.: 1546 AF XY: 0.0679 AC XY: 17905 AN XY: 263836

African (AFR) AF: 0.0193 AC: 278 AN: 14402

American (AMR) AF: 0.0462 AC: 1375 AN: 29786

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 1987 AN: 15812

East Asian (EAS) AF: 0.0000323 AC: 1 AN: 30988

South Asian (SAS) AF: 0.0241 AC: 1253 AN: 51960

European-Finnish (FIN) AF: 0.128 AC: 5051 AN: 39536

Middle Eastern (MID) AF: 0.108 AC: 244 AN: 2266

European-Non Finnish (NFE) AF: 0.0785 AC: 22537 AN: 286990

Other (OTH) AF: 0.0733 AC: 2018 AN: 27526

GnomAD4 genome AF: 0.0594 AC: 9017 AN: 151732 Hom.: 375 Cov.: 32 AF XY: 0.0608 AC XY: 4513 AN XY: 74188

African (AFR) AF: 0.0166 AC: 689 AN: 41488

American (AMR) AF: 0.0561 AC: 857 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3464

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5132

South Asian (SAS) AF: 0.0221 AC: 106 AN: 4794

European-Finnish (FIN) AF: 0.130 AC: 1367 AN: 10482

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.0785 AC: 5323 AN: 67782

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0227 Hom.: 21

Asia WGS AF: 0.0130 AC: 47 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	-0.89
CADD	Benign	4.9
DANN	Benign	0.69
PhyloP100		-1.3
PromoterAI		0.068	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41308844; hg19: chr5-52285098;