rs4509693

Variant names:

• chr10-100741814-C-T
• rs4509693
• NM_001304569.2:c.26-4379C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001304569.2(PAX2):​c.26-4379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,248 control chromosomes in the GnomAD database, including 48,768 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 0.80 (48768 hom., cov: 34)
• Consequence: PAX2 NM_001304569.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 16 publications found

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, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304569.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX2	NM_001304569.2		c.26-4379C>T		intron	N/A	NP_001291498.1	A0A9L9PYK3
	PAX2	NM_001374303.1		c.26-4379C>T		intron	N/A	NP_001361232.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX2	ENST00000707078.1		c.26-4379C>T		intron	N/A	ENSP00000516729.1	A0A9L9PYK3
	PAX2	ENST00000679374.1		c.25+6081C>T		intron	N/A	ENSP00000506041.1	A0A7P0TAC9
	PAX2	ENST00000553492.5	TSL:4	n.131+6081C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121449 AN: 152130 Hom.: 48721 Cov.: 34

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: 0.861

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.777

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.798 AC: 121552 AN: 152248 Hom.: 48768 Cov.: 34 AF XY: 0.807 AC XY: 60048 AN XY: 74452

African (AFR) AF: 0.747 AC: 31001 AN: 41500

American (AMR) AF: 0.814 AC: 12465 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2756 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5178 AN: 5188

South Asian (SAS) AF: 0.919 AC: 4442 AN: 4834

European-Finnish (FIN) AF: 0.861 AC: 9150 AN: 10624

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53928 AN: 68004

Other (OTH) AF: 0.779 AC: 1646 AN: 2112

Alfa AF: 0.798 Hom.: 103641

Bravo AF: 0.790

Asia WGS AF: 0.947 AC: 3290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Benign	0.84
PhyloP100		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4509693; hg19: chr10-102501571;