Genetic Variant PAX2:c.43+1279C>T (chr10-100747582-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000278.5(PAX2):c.43+1279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 980,140 control chromosomes in the GnomAD database, including 297,255 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 0.79 ( 47034 hom., cov: 29)

Exomes 𝑓: 0.78 ( 250221 hom. )

Consequence

PAX2
NM_000278.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

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+1279C>T		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+1279C>T		intron_variant	Intron 1 of 9	1	NM_000278.5	ENSP00000347385.3		Q02962-3

Frequencies

GnomAD3 genomes

AF:

0.786

AC:

119083

AN:

151492

Hom.:

46991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.753

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.803

Gnomad ASJ

AF:

0.768

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.918

Gnomad FIN

AF:

0.848

Gnomad MID

AF:

0.774

Gnomad NFE

AF:

0.769

Gnomad OTH

AF:

0.768

GnomAD4 exome

AF:

0.776

AC:

643248

AN:

828530

Hom.:

250221

Cov.:

AF XY:

0.776

AC XY:

296884

AN XY:

382746

show subpopulations

African (AFR)

AF:

0.740

AC:

11609

AN:

15692

American (AMR)

AF:

0.837

AC:

819

AN:

978

Ashkenazi Jewish (ASJ)

AF:

0.763

AC:

3906

AN:

5122

East Asian (EAS)

AF:

0.999

AC:

3613

AN:

3618

South Asian (SAS)

AF:

0.921

AC:

15114

AN:

16402

European-Finnish (FIN)

AF:

0.833

AC:

230

AN:

276

Middle Eastern (MID)

AF:

0.730

AC:

1175

AN:

1610

European-Non Finnish (NFE)

AF:

0.773

AC:

585315

AN:

757686

Other (OTH)

AF:

0.791

AC:

21467

AN:

27146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

6316

12632

18948

25264

31580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19128

38256

57384

76512

95640

<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:

0.786

AC:

119184

AN:

151610

Hom.:

47034

Cov.:

AF XY:

0.795

AC XY:

58911

AN XY:

74070

show subpopulations

African (AFR)

AF:

0.753

AC:

31100

AN:

41286

American (AMR)

AF:

0.804

AC:

12267

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.768

AC:

2662

AN:

3464

East Asian (EAS)

AF:

0.998

AC:

5102

AN:

5112

South Asian (SAS)

AF:

0.918

AC:

4386

AN:

4780

European-Finnish (FIN)

AF:

0.848

AC:

8883

AN:

10474

Middle Eastern (MID)

AF:

0.777

AC:

227

AN:

292

European-Non Finnish (NFE)

AF:

0.769

AC:

52256

AN:

67930

Other (OTH)

AF:

0.771

AC:

1617

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1274

2548

3823

5097

6371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.782

Hom.:

6762

Bravo

AF:

0.778

Asia WGS

AF:

0.943

AC:

3274

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

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