rs11190698

Variant names:

• chr10-100776250-A-C
• rs11190698
• NM_000278.5:c.411-3248A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000278.5(PAX2):​c.411-3248A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,616 control chromosomes in the GnomAD database, including 2,801 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 0.18 (2801 hom., cov: 32)
• Consequence: PAX2 NM_000278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 4 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, 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX2	NM_000278.5	c.411-3248A>C		intron_variant	Intron 3 of 9	ENST00000355243.8	NP_000269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000355243.8	c.411-3248A>C		intron_variant	Intron 3 of 9	1	NM_000278.5	ENSP00000347385.3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27820 AN: 151500 Hom.: 2802 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.00428

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.184 AC: 27826 AN: 151616 Hom.: 2801 Cov.: 32 AF XY: 0.176 AC XY: 13015 AN XY: 74078

African (AFR) AF: 0.159 AC: 6572 AN: 41312

American (AMR) AF: 0.162 AC: 2465 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.00429 AC: 22 AN: 5126

South Asian (SAS) AF: 0.189 AC: 904 AN: 4792

European-Finnish (FIN) AF: 0.128 AC: 1341 AN: 10490

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.222 AC: 15103 AN: 67888

Other (OTH) AF: 0.197 AC: 415 AN: 2104

Alfa AF: 0.212 Hom.: 1843

Bravo AF: 0.183

Asia WGS AF: 0.0810 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.62
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11190698; hg19: chr10-102536007;