Genetic Variant NM_002728.6:c.366+45T>C (chr11-57388965-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002728.6(PRG2):c.366+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,585,392 control chromosomes in the GnomAD database, including 150,040 homozygotes. 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 0.37 ( 11192 hom., cov: 31)

Exomes 𝑓: 0.43 ( 138848 hom. )

Consequence

PRG2
NM_002728.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

18 publications found

Variant links:

Genes affected

PRG2 (HGNC:9362): (proteoglycan 2, pro eosinophil major basic protein) The protein encoded by this gene is the predominant constituent of the crystalline core of the eosinophil granule. High levels of the proform of this protein are also present in placenta and pregnancy serum, where it exists as a complex with several other proteins including pregnancy-associated plasma protein A (PAPPA), angiotensinogen (AGT), and C3dg. This protein may be involved in antiparasitic defense mechanisms as a cytotoxin and helminthotoxin, and in immune hypersensitivity reactions. The encoded protein contains a peptide that displays potent antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and fungi. It is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

PRG2 links:

ENSG00000254979 (HGNC:):

ENSG00000254979 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRG2	NM_002728.6 link	c.366+45T>C	intron_variant	Intron 3 of 5	ENST00000311862.10	NP_002719.3	P13727-1
PRG2	NM_001302926.2 link	c.366+45T>C	intron_variant	Intron 3 of 5		NP_001289855.1	P13727-1
PRG2	NM_001302927.2 link	c.366+45T>C	intron_variant	Intron 3 of 5		NP_001289856.1	P13727-1
PRG2	NM_001243245.3 link	c.333+78T>C	intron_variant	Intron 3 of 5		NP_001230174.1	P13727-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRG2	ENST00000311862.10 link	c.366+45T>C		intron_variant	Intron 3 of 5	1	NM_002728.6	ENSP00000312134.5		P13727-1
ENSG00000254979	ENST00000529411.1 link	c.*45T>C		downstream_gene_variant		4		ENSP00000431536.1		H0YCG3

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56695

AN:

151820

Hom.:

11192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.381

GnomAD2 exomes

AF:

0.365

AC:

84115

AN:

230746

AF XY:

0.372

show subpopulations

Gnomad AFR exome

AF:

0.276

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.370

Gnomad EAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.380

GnomAD4 exome

AF:

0.434

AC:

621711

AN:

1433452

Hom.:

138848

Cov.:

AF XY:

0.432

AC XY:

307018

AN XY:

710830

show subpopulations

African (AFR)

AF:

0.266

AC:

8780

AN:

33024

American (AMR)

AF:

0.197

AC:

8599

AN:

43632

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

8952

AN:

24394

East Asian (EAS)

AF:

0.289

AC:

11403

AN:

39520

South Asian (SAS)

AF:

0.307

AC:

25176

AN:

82010

European-Finnish (FIN)

AF:

0.409

AC:

19655

AN:

48100

Middle Eastern (MID)

AF:

0.340

AC:

1715

AN:

5040

European-Non Finnish (NFE)

AF:

0.468

AC:

513829

AN:

1098426

Other (OTH)

AF:

0.398

AC:

23602

AN:

59306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

19915

39831

59746

79662

99577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15110

30220

45330

60440

75550

<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:

0.373

AC:

56724

AN:

151940

Hom.:

11192

Cov.:

AF XY:

0.369

AC XY:

27378

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.280

AC:

11587

AN:

41428

American (AMR)

AF:

0.278

AC:

4244

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1244

AN:

3464

East Asian (EAS)

AF:

0.247

AC:

1272

AN:

5146

South Asian (SAS)

AF:

0.295

AC:

1418

AN:

4814

European-Finnish (FIN)

AF:

0.400

AC:

4213

AN:

10542

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.463

AC:

31446

AN:

67972

Other (OTH)

AF:

0.377

AC:

792

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1792

3584

5375

7167

8959

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:

0.426

Hom.:

31438

Bravo

AF:

0.360

Asia WGS

AF:

0.232

AC:

809

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.67

(source)

DANN

Benign

0.60

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over