Genetic Variant ITGA2-AS1:n.189+822C>A (chr5-52989268-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.27

Publications

3 publications found

Variant links:

Genes affected

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

ITGA2-AS1 links:

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

ITGA2 links:

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new If you want to explore the variant's impact on the transcript ENST00000505701.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
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.:

show subpopulations

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

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1512

3025

4537

6050

7562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0594

AC:

9017

AN:

151732

Hom.:

375

Cov.:

AF XY:

0.0608

AC XY:

4513

AN XY:

74188

show subpopulations

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:

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.0785

AC:

5323

AN:

67782

Other (OTH)

AF:

0.0639

AC:

135

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

362

723

1085

1446

1808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0227

Hom.:

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.9

(source)

DANN

Benign

0.69

PhyloP100

-1.3

PromoterAI

0.068

Neutral

(source)

Splicing

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over