dbSNP rs57674800: ITGA2:c.*3599_*3600insTATATAAACAACTTTGTAGGACTAT (chr5-53094196-A-AATTATATAAACAACTTTGTAGGACT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002203.4(ITGA2):c.*3599_*3600insTATATAAACAACTTTGTAGGACTAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.35 ( 9517 hom., cov: 0)

Exomes 𝑓: 0.50 ( 3 hom. )

Consequence

ITGA2
NM_002203.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.877

Publications

3 publications found

Variant links:

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)

ITGA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.402 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGA2	NM_002203.4	MANE Select	c.3599_3600insTATATAAACAACTTTGTAGGACTAT	3_prime_UTR	Exon 30 of 30	NP_002194.2	P17301
ITGA2	NR_073103.2		n.7159_7160insTATATAAACAACTTTGTAGGACTAT	non_coding_transcript_exon	Exon 29 of 29
ITGA2	NR_073104.2		n.7120_7121insTATATAAACAACTTTGTAGGACTAT	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.3599_3600insTATATAAACAACTTTGTAGGACTAT		3_prime_UTR	Exon 30 of 30	ENSP00000296585.5	P17301

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53460

AN:

151866

Hom.:

9513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.357

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.550

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.352

AC:

53478

AN:

151978

Hom.:

9517

Cov.:

AF XY:

0.354

AC XY:

26294

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.286

AC:

11850

AN:

41460

American (AMR)

AF:

0.411

AC:

6272

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1190

AN:

3470

East Asian (EAS)

AF:

0.313

AC:

1622

AN:

5174

South Asian (SAS)

AF:

0.347

AC:

1669

AN:

4808

European-Finnish (FIN)

AF:

0.401

AC:

4226

AN:

10548

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.374

AC:

25424

AN:

67928

Other (OTH)

AF:

0.358

AC:

756

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1745

3491

5236

6982

8727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.221

Hom.:

341

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Platelet-type bleeding disorder 9 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.88

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over