rs11190688

Variant names:

• chr10-100764713-G-A
• rs11190688
• NM_000278.5:c.410+13822G>A

Variant summary

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

The NM_000278.5(PAX2):​c.410+13822G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,120 control chromosomes in the GnomAD database, including 2,419 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 0.16 (2419 hom., cov: 32)
• Consequence: PAX2 NM_000278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX2	NM_000278.5	c.410+13822G>A		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.410+13822G>A		intron_variant	Intron 3 of 9	1	NM_000278.5	ENSP00000347385.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23928 AN: 152002 Hom.: 2419 Cov.: 32

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.157 AC: 23920 AN: 152120 Hom.: 2419 Cov.: 32 AF XY: 0.151 AC XY: 11253 AN XY: 74382

African (AFR) AF: 0.0556 AC: 2306 AN: 41492

American (AMR) AF: 0.155 AC: 2363 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 748 AN: 3468

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5168

South Asian (SAS) AF: 0.189 AC: 908 AN: 4814

European-Finnish (FIN) AF: 0.134 AC: 1414 AN: 10580

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15505 AN: 68004

Other (OTH) AF: 0.187 AC: 395 AN: 2110

Alfa AF: 0.210 Hom.: 4480

Bravo AF: 0.154

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.55
PhyloP100		0.088
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: rs11190688; hg19: chr10-102524470;