dbSNP rs2303127: ITGA2:c.1312+12T>C (chr5-53060024-T-C) – 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 NM_002203.4(ITGA2):c.1312+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,610,664 control chromosomes in the GnomAD database, including 126,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10284 hom., cov: 32)

Exomes 𝑓: 0.40 ( 116085 hom. )

Consequence

ITGA2
NM_002203.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.510

Publications

10 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-53060024-T-C is Benign according to our data. Variant chr5-53060024-T-C is described in ClinVar as Benign. ClinVar VariationId is 353751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.418 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.1312+12T>C	intron	N/A	NP_002194.2	P17301
ITGA2	NR_073103.2		n.1429+12T>C	intron	N/A
ITGA2	NR_073104.2		n.1429+12T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.1312+12T>C	intron	N/A	ENSP00000296585.5	P17301
ITGA2	ENST00000509814.5	TSL:1	n.1312+12T>C	intron	N/A	ENSP00000424397.1	E7EMF1
ITGA2	ENST00000509960.5	TSL:1	n.1312+12T>C	intron	N/A	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55352

AN:

151610

Hom.:

10285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.377

GnomAD2 exomes

AF:

0.388

AC:

97064

AN:

250468

AF XY:

0.387

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.397

AC:

578635

AN:

1458936

Hom.:

116085

Cov.:

AF XY:

0.396

AC XY:

287207

AN XY:

725874

show subpopulations

African (AFR)

AF:

0.282

AC:

9425

AN:

33368

American (AMR)

AF:

0.454

AC:

20239

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

10126

AN:

26040

East Asian (EAS)

AF:

0.358

AC:

14181

AN:

39592

South Asian (SAS)

AF:

0.366

AC:

31560

AN:

86202

European-Finnish (FIN)

AF:

0.397

AC:

21172

AN:

53336

Middle Eastern (MID)

AF:

0.381

AC:

2192

AN:

5748

European-Non Finnish (NFE)

AF:

0.402

AC:

446238

AN:

1109878

Other (OTH)

AF:

0.390

AC:

23502

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

17714

35429

53143

70858

88572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13820

27640

41460

55280

69100

<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:

0.365

AC:

55372

AN:

151728

Hom.:

10284

Cov.:

AF XY:

0.365

AC XY:

27064

AN XY:

74138

show subpopulations

African (AFR)

AF:

0.283

AC:

11739

AN:

41434

American (AMR)

AF:

0.427

AC:

6487

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1286

AN:

3468

East Asian (EAS)

AF:

0.305

AC:

1559

AN:

5108

South Asian (SAS)

AF:

0.352

AC:

1698

AN:

4830

European-Finnish (FIN)

AF:

0.395

AC:

4174

AN:

10560

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27142

AN:

67822

Other (OTH)

AF:

0.377

AC:

796

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1805

3610

5414

7219

9024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.392

Hom.:

4041

Bravo

AF:

0.366

Asia WGS

AF:

0.335

AC:

1163

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Platelet-type bleeding disorder 9 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.0

(source)

DANN

Benign

0.63

PhyloP100

-0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over