10-100760418-G-A

Variant names:

• chr10-100760418-G-A
• rs11599825
• NM_000278.5:c.410+9527G>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+9527G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,174 control chromosomes in the GnomAD database, including 2,368 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 (2368 hom., cov: 32)
• Consequence: PAX2 NM_000278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 1 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 = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX2	NM_000278.5	c.410+9527G>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+9527G>A		intron_variant	Intron 3 of 9	1	NM_000278.5	ENSP00000347385.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23738 AN: 152056 Hom.: 2368 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.156 AC: 23730 AN: 152174 Hom.: 2368 Cov.: 32 AF XY: 0.150 AC XY: 11153 AN XY: 74382

African (AFR) AF: 0.0552 AC: 2292 AN: 41530

American (AMR) AF: 0.153 AC: 2346 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3472

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5176

South Asian (SAS) AF: 0.187 AC: 900 AN: 4824

European-Finnish (FIN) AF: 0.133 AC: 1408 AN: 10598

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15372 AN: 67960

Other (OTH) AF: 0.185 AC: 392 AN: 2114

Alfa AF: 0.177 Hom.: 375

Bravo AF: 0.152

Asia WGS AF: 0.0720 AC: 252 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	0.59
DANN	Benign	0.64
PhyloP100		-1.3
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: rs11599825; hg19: chr10-102520175;