rs1800897

chr10-100809115-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000278.5(PAX2):c.798C>T(p.Asn266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 1,611,838 control chromosomes in the GnomAD database, including 6,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2438 hom., cov: 32)
  • Exomes 𝑓: 0.051 (3984 hom.)
• Consequence: PAX2 NM_000278.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: -0.215

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 10-100809115-C-T is Benign according to our data. Variant chr10-100809115-C-T is described in ClinVar as [Benign]. Clinvar id is 156298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-100809115-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.215 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX2	NM_000278.5	c.798C>T	p.Asn266=	synonymous_variant	7/10	ENST00000355243.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX2	ENST00000355243.8	c.798C>T	p.Asn266=	synonymous_variant	7/10	1	NM_000278.5	P4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18930 AN: 151972 Hom.: 2432 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0951

GnomAD3 exomes AF: 0.0744 AC: 18703 AN: 251364 Hom.: 1442 AF XY: 0.0706 AC XY: 9587 AN XY: 135864

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.0697

Gnomad ASJ exome AF: 0.0217

Gnomad EAS exome AF: 0.0975

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.0397

Gnomad OTH exome AF: 0.0534

GnomAD4 exome AF: 0.0515 AC: 75169 AN: 1459748 Hom.: 3984 Cov.: 31 AF XY: 0.0522 AC XY: 37890 AN XY: 726358

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.0667

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.0993

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0254

Gnomad4 NFE exome AF: 0.0367

Gnomad4 OTH exome AF: 0.0671

GnomAD4 genome AF: 0.125 AC: 18975 AN: 152090 Hom.: 2438 Cov.: 32 AF XY: 0.124 AC XY: 9200 AN XY: 74348

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.0694

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.0903

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0617 Hom.: 974

Bravo AF: 0.137

Asia WGS AF: 0.146 AC: 510 AN: 3478

EpiCase AF: 0.0412

EpiControl AF: 0.0372

ClinVar

Significance: Benign

Submissions summary: Benign:6 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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+	-	- -

Renal coloboma syndrome;C4014925:Focal segmental glomerulosclerosis 7 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 29, 2021	- -

not provided Benign:1 Other: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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	1.1
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs1800897; hg19: chr10-102568872; COSMIC: COSV62292931; COSMIC: COSV62292931;