chr10-100768055-A-T

Variant names:

• chr10-100768055-A-T
• rs11190693
• NM_000278.5:c.411-11443A>T

Variant summary

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

The NM_000278.5(PAX2):​c.411-11443A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 148,494 control chromosomes in the GnomAD database, including 2,394 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 (2394 hom., cov: 30)
• Consequence: PAX2 NM_000278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• Publications: 3 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=-0.77).
• 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.411-11443A>T		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.411-11443A>T		intron_variant	Intron 3 of 9	1	NM_000278.5	ENSP00000347385.3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 23730 AN: 148378 Hom.: 2394 Cov.: 30

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.00452

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.160 AC: 23722 AN: 148494 Hom.: 2394 Cov.: 30 AF XY: 0.154 AC XY: 11128 AN XY: 72052

African (AFR) AF: 0.0565 AC: 2261 AN: 40016

American (AMR) AF: 0.162 AC: 2346 AN: 14460

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 740 AN: 3454

East Asian (EAS) AF: 0.00453 AC: 23 AN: 5072

South Asian (SAS) AF: 0.187 AC: 886 AN: 4730

European-Finnish (FIN) AF: 0.139 AC: 1367 AN: 9842

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15453 AN: 67662

Other (OTH) AF: 0.190 AC: 390 AN: 2058

Alfa AF: 0.183 Hom.: 381

Bravo AF: 0.154

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.74
PhyloP100		0.37
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: rs11190693; hg19: chr10-102527812;