rs4509693

Positions:

• chr10-100741814-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX2	NM_001304569.2	c.26-4379C>T		intron_variant			NP_001291498.1
PAX2	NM_001374303.1	c.26-4379C>T		intron_variant			NP_001361232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000679374.1	c.25+6081C>T		intron_variant				ENSP00000506041
PAX2	ENST00000707078.1	c.26-4379C>T		intron_variant				ENSP00000516729
PAX2	ENST00000553492.5	n.131+6081C>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.779

Alfa AF: 0.802 Hom.: 71537

Bravo AF: 0.790

Asia WGS AF: 0.947 AC: 3290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4509693; hg19: chr10-102501571;