Genetic Variant PAX2:c.25+31A>G (chr10-100735764-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001304569.2(PAX2):c.25+31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,027,292 control chromosomes in the GnomAD database, including 329,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49012 hom., cov: 31)

Exomes 𝑓: 0.80 ( 280970 hom. )

Consequence

PAX2
NM_001304569.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.70

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-100735764-A-G is Benign according to our data. Variant chr10-100735764-A-G is described in ClinVar as [Benign]. Clinvar id is 1326988.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_001304569.2 link	c.25+31A>G		intron_variant	Intron 1 of 10		NP_001291498.1	Q02962
PAX2	NM_001374303.1 link	c.25+31A>G		intron_variant	Intron 1 of 2		NP_001361232.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
PAX2	ENST00000707078.1 link	c.25+31A>G	intron_variant	Intron 1 of 10		ENSP00000516729.1	A0A9L9PYK3
PAX2	ENST00000679374.1 link	c.25+31A>G	intron_variant	Intron 1 of 9		ENSP00000506041.1	A0A7P0TAC9
PAX2	ENST00000553492.5 link	n.131+31A>G	intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.801

AC:

121702

AN:

151862

Hom.:

48964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.758

Gnomad AMI

AF:

0.840

Gnomad AMR

AF:

0.814

Gnomad ASJ

AF:

0.794

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.920

Gnomad FIN

AF:

0.863

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.793

Gnomad OTH

AF:

0.777

GnomAD4 exome

AF:

0.801

AC:

700696

AN:

875312

Hom.:

280970

Cov.:

AF XY:

0.800

AC XY:

323578

AN XY:

404436

show subpopulations

Gnomad4 AFR exome

AF:

0.742

Gnomad4 AMR exome

AF:

0.831

Gnomad4 ASJ exome

AF:

0.789

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.923

Gnomad4 FIN exome

AF:

0.839

Gnomad4 NFE exome

AF:

0.796

Gnomad4 OTH exome

AF:

0.807

GnomAD4 genome

AF:

0.801

AC:

121806

AN:

151980

Hom.:

49012

Cov.:

AF XY:

0.809

AC XY:

60141

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.758

Gnomad4 AMR

AF:

0.815

Gnomad4 ASJ

AF:

0.794

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.920

Gnomad4 FIN

AF:

0.863

Gnomad4 NFE

AF:

0.793

Gnomad4 OTH

AF:

0.780

Alfa

AF:

0.802

Hom.:

6081

Bravo

AF:

0.794

Asia WGS

AF:

0.947

AC:

3291

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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:1

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.036

DANN

Benign

0.25

Splicing

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