Genetic Variant ENST00000503559.1: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 ENST00000503559.1(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
ENST00000503559.1 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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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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4 link	c.-222C>A		upstream_gene_variant		ENST00000296585.10	NP_002194.2	P17301

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10 link	c.-222C>A		upstream_gene_variant		1	NM_002203.4	ENSP00000296585.5		P17301

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over