Genetic Variant ITGA2-AS1:n.189+843G>T (chr5-52989247-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000505701.5(ITGA2-AS1):n.189+843G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000714 in 139,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITGA2-AS1
ENST00000505701.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.489

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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+843G>T	intron	N/A
ITGA2	NM_002203.4	MANE Select	c.-222C>A	upstream_gene	N/A	NP_002194.2	P17301
ITGA2	NR_073103.2		n.-105C>A	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ITGA2-AS1	ENST00000503559.1	TSL:5	n.189+843G>T	intron	N/A
ITGA2-AS1	ENST00000505701.5	TSL:4	n.189+843G>T	intron	N/A
ITGA2-AS1	ENST00000662246.1		n.75+843G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000714

AC:

AN:

139978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000156

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

446076

Hom.:

AF XY:

0.00

AC XY:

AN XY:

234920

African (AFR)

AF:

0.00

AC:

AN:

12342

American (AMR)

AF:

0.00

AC:

AN:

21914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13662

East Asian (EAS)

AF:

0.00

AC:

AN:

29416

South Asian (SAS)

AF:

0.00

AC:

AN:

46222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1950

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

262146

Other (OTH)

AF:

0.00

AC:

AN:

25402

GnomAD4 genome

AF:

0.00000714

AC:

AN:

139978

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38986

American (AMR)

AF:

0.00

AC:

AN:

14100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3324

East Asian (EAS)

AF:

0.00

AC:

AN:

4086

South Asian (SAS)

AF:

0.00

AC:

AN:

4062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000156

AC:

AN:

63960

Other (OTH)

AF:

0.00

AC:

AN:

1934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.1

(source)

DANN

Benign

0.73

PhyloP100

-0.49

PromoterAI

-0.22

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over