Genetic Variant PXDN:c.1568-19C>G (chr2-1662203-G-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_012293.3(PXDN):c.1568-19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,556,176 control chromosomes in the GnomAD database, including 2,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 1157 hom., cov: 33)

Exomes 𝑓: 0.014 ( 1330 hom. )

Consequence

PXDN
NM_012293.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.382

Publications

3 publications found

Variant links:

Genes affected

PXDN (HGNC:14966): (peroxidasin) This gene encodes a heme-containing peroxidase that is secreted into the extracellular matrix. It is involved in extracellular matrix formation, and may function in the physiological and pathological fibrogenic response in fibrotic kidney. Mutations in this gene cause corneal opacification and other ocular anomalies, and also microphthalmia and anterior segment dysgenesis. [provided by RefSeq, Aug 2014]

PXDN Gene-Disease associations (from GenCC):

anterior segment dysgenesis 7
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

PXDN 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=-0.94).

BP6

Variant 2-1662203-G-C is Benign according to our data. Variant chr2-1662203-G-C is described in ClinVar as Benign. ClinVar VariationId is 260219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	NM_012293.3	MANE Select	c.1568-19C>G		intron	N/A	NP_036425.1	Q92626-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PXDN	ENST00000252804.9	TSL:1 MANE Select	c.1568-19C>G	intron	N/A	ENSP00000252804.4	Q92626-1
PXDN	ENST00000433670.5	TSL:1	c.1553-19C>G	intron	N/A	ENSP00000402738.1	H7C1W1
PXDN	ENST00000857505.1		c.1496-19C>G	intron	N/A	ENSP00000527564.1

Frequencies

GnomAD3 genomes

AF:

0.0747

AC:

11372

AN:

152168

Hom.:

1154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0277

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.0412

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00294

Gnomad OTH

AF:

0.0554

GnomAD2 exomes

AF:

0.0319

AC:

5540

AN:

173914

AF XY:

0.0274

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.0430

Gnomad NFE exome

AF:

0.00306

Gnomad OTH exome

AF:

0.0248

GnomAD4 exome

AF:

0.0139

AC:

19562

AN:

1403890

Hom.:

1330

Cov.:

AF XY:

0.0130

AC XY:

9023

AN XY:

694528

show subpopulations

African (AFR)

AF:

0.241

AC:

7772

AN:

32212

American (AMR)

AF:

0.0148

AC:

552

AN:

37236

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

297

AN:

25248

East Asian (EAS)

AF:

0.107

AC:

3999

AN:

37234

South Asian (SAS)

AF:

0.00714

AC:

572

AN:

80142

European-Finnish (FIN)

AF:

0.0404

AC:

2042

AN:

50506

Middle Eastern (MID)

AF:

0.0216

AC:

123

AN:

5702

European-Non Finnish (NFE)

AF:

0.00230

AC:

2479

AN:

1077220

Other (OTH)

AF:

0.0296

AC:

1726

AN:

58390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

942

1884

2826

3768

4710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.0748

AC:

11392

AN:

152286

Hom.:

1157

Cov.:

AF XY:

0.0742

AC XY:

5529

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.228

AC:

9475

AN:

41528

American (AMR)

AF:

0.0276

AC:

423

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3468

East Asian (EAS)

AF:

0.125

AC:

645

AN:

5176

South Asian (SAS)

AF:

0.00973

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0412

AC:

438

AN:

10632

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00293

AC:

199

AN:

68030

Other (OTH)

AF:

0.0558

AC:

118

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

457

914

1370

1827

2284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0344

Hom.:

Bravo

AF:

0.0813

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Anterior segment dysgenesis 7 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.45

(source)

DANN

Benign

0.29

PhyloP100

-0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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