rs1800898

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

PAX2 (HGNC:):

PAX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 156300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-100809226-A-C is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
PAX2	NM_000278.5 linkuse as main transcript	c.909A>C	p.Pro303Pro	synonymous_variant	7/10	ENST00000355243.8	NP_000269.3	Q02962-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000355243.8 linkuse as main transcript	c.909A>C	p.Pro303Pro	synonymous_variant	7/10	1	NM_000278.5	ENSP00000347385.3		Q02962-3

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

GnomAD3 exomes

AF:

0.281

AC:

70589

AN:

251066

Hom.:

12555

AF XY:

0.280

AC XY:

37976

AN XY:

135748

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 SAS exome

AF:

0.323

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

Gnomad4 AFR exome

AF:

0.763

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.324

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.394

AC:

59982

AN:

152110

Hom.:

15576

Cov.:

AF XY:

0.385

AC XY:

28589

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.742

Gnomad4 AMR

AF:

0.275

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.0937

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.296

Hom.:

8204

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	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. -

not provided

Benign:2Other:1

not provided, no classification provided	literature only	ClinVar Staff, National Center for Biotechnology Information (NCBI)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Renal coloboma syndrome

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Focal segmental glomerulosclerosis 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Renal coloboma syndrome;C4014925:Focal segmental glomerulosclerosis 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.63

DANN

Benign

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over