rs1800898

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000278.5(PAX2):c.909A>C(p.Pro303Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,612,774 control chromosomes in the GnomAD database, including 81,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 15576 hom., cov: 32)

Exomes 𝑓: 0.29 ( 66047 hom. )

Consequence

PAX2
NM_000278.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: -0.735

Publications

17 publications found

Variant links:

Genes affected

PAX2 (HGNC:8616): (paired box 2) PAX2 encodes paired box gene 2, one of many human homologues of the Drosophila melanogaster gene prd. The central feature of this transcription factor gene family is the conserved DNA-binding paired box domain. PAX2 is believed to be a target of transcriptional supression by the tumor suppressor gene WT1. Mutations within PAX2 have been shown to result in optic nerve colobomas and renal hypoplasia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2014]

PAX2 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis 7
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
renal coloboma syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PAX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 10-100809226-A-C is Benign according to our data. Variant chr10-100809226-A-C is described in ClinVar as Benign. ClinVar VariationId is 156300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.735 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX2	NM_000278.5 link	c.909A>C	p.Pro303Pro	synonymous_variant	Exon 7 of 10	ENST00000355243.8	NP_000269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000355243.8 link	c.909A>C	p.Pro303Pro	synonymous_variant	Exon 7 of 10	1	NM_000278.5	ENSP00000347385.3

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59901

AN:

151992

Hom.:

15544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.742

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.0939

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.364

GnomAD2 exomes

AF:

0.281

AC:

70589

AN:

251066

AF XY:

0.280

show subpopulations

Gnomad AFR exome

AF:

0.749

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.0986

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.272

GnomAD4 exome

AF:

0.287

AC:

419175

AN:

1460664

Hom.:

66047

Cov.:

AF XY:

0.287

AC XY:

208795

AN XY:

726666

show subpopulations

African (AFR)

AF:

0.763

AC:

25510

AN:

33452

American (AMR)

AF:

0.200

AC:

8953

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

6593

AN:

26124

East Asian (EAS)

AF:

0.100

AC:

3986

AN:

39680

South Asian (SAS)

AF:

0.324

AC:

27940

AN:

86232

European-Finnish (FIN)

AF:

0.182

AC:

9679

AN:

53130

Middle Eastern (MID)

AF:

0.408

AC:

2353

AN:

5768

European-Non Finnish (NFE)

AF:

0.284

AC:

315629

AN:

1111224

Other (OTH)

AF:

0.307

AC:

18532

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

14806

29612

44418

59224

74030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10652

21304

31956

42608

53260

<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:

0.394

AC:

59982

AN:

152110

Hom.:

15576

Cov.:

AF XY:

0.385

AC XY:

28589

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.742

AC:

30766

AN:

41482

American (AMR)

AF:

0.275

AC:

4207

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

865

AN:

3470

East Asian (EAS)

AF:

0.0937

AC:

485

AN:

5174

South Asian (SAS)

AF:

0.306

AC:

1469

AN:

4808

European-Finnish (FIN)

AF:

0.187

AC:

1986

AN:

10594

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19013

AN:

67976

Other (OTH)

AF:

0.364

AC:

768

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1495

2991

4486

5982

7477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.316

Hom.:

14066

Bravo

AF:

0.416

Asia WGS

AF:

0.251

AC:

874

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.299

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 39% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 36. Only high quality variants are reported. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2Other:1

ClinVar Staff, National Center for Biotechnology Information (NCBI)

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Renal coloboma syndrome

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis 7

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Renal coloboma syndrome;C4014925:Focal segmental glomerulosclerosis 7

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.63

(source)

DANN

Benign

0.41

PhyloP100

-0.73

Mutation Taster

=98/2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over