10-100746313-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000278.5(PAX2):c.43+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 1,576,532 control chromosomes in the GnomAD database, including 520,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48725 hom., cov: 33)

Exomes 𝑓: 0.81 ( 471896 hom. )

Consequence

PAX2
NM_000278.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.77

Publications

11 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 10-100746313-G-C is Benign according to our data. Variant chr10-100746313-G-C is described in ClinVar as Benign. ClinVar VariationId is 94387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX2	NM_000278.5 link	c.43+10G>C		intron_variant	Intron 1 of 9	ENST00000355243.8	NP_000269.3	Q02962-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000355243.8 link	c.43+10G>C		intron_variant	Intron 1 of 9	1	NM_000278.5	ENSP00000347385.3		Q02962-3

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121385

AN:

152074

Hom.:

48678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.747

Gnomad AMI

AF:

0.827

Gnomad AMR

AF:

0.814

Gnomad ASJ

AF:

0.794

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.919

Gnomad FIN

AF:

0.863

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.793

Gnomad OTH

AF:

0.778

GnomAD2 exomes

AF:

0.838

AC:

208401

AN:

248608

AF XY:

0.840

show subpopulations

Gnomad AFR exome

AF:

0.749

Gnomad AMR exome

AF:

0.856

Gnomad ASJ exome

AF:

0.792

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.861

Gnomad NFE exome

AF:

0.797

Gnomad OTH exome

AF:

0.815

GnomAD4 exome

AF:

0.812

AC:

1157089

AN:

1424340

Hom.:

471896

Cov.:

AF XY:

0.815

AC XY:

579178

AN XY:

710880

show subpopulations

African (AFR)

AF:

0.737

AC:

24077

AN:

32662

American (AMR)

AF:

0.850

AC:

37973

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

20487

AN:

25922

East Asian (EAS)

AF:

1.00

AC:

39507

AN:

39526

South Asian (SAS)

AF:

0.920

AC:

78721

AN:

85574

European-Finnish (FIN)

AF:

0.855

AC:

45613

AN:

53342

Middle Eastern (MID)

AF:

0.787

AC:

4484

AN:

5694

European-Non Finnish (NFE)

AF:

0.796

AC:

858329

AN:

1077858

Other (OTH)

AF:

0.811

AC:

47898

AN:

59084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

11027

22054

33080

44107

55134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19952

39904

59856

79808

99760

<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:

0.798

AC:

121488

AN:

152192

Hom.:

48725

Cov.:

AF XY:

0.807

AC XY:

60031

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.747

AC:

30994

AN:

41508

American (AMR)

AF:

0.814

AC:

12458

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.794

AC:

2756

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5157

AN:

5168

South Asian (SAS)

AF:

0.919

AC:

4431

AN:

4822

European-Finnish (FIN)

AF:

0.863

AC:

9150

AN:

10608

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.793

AC:

53910

AN:

68000

Other (OTH)

AF:

0.781

AC:

1648

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1296

2592

3889

5185

6481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.779

Hom.:

5211

Bravo

AF:

0.790

Asia WGS

AF:

0.946

AC:

3289

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 20, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 97% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 90. Only high quality variants are reported. -

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

- -

not provided

Benign:2

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

- -

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

-0.45

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

1.8

PromoterAI

0.022

Neutral

(source)

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over