10-100776250-A-C

Position:

• chr10-100776250-A-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
PAX2	NM_000278.5	c.411-3248A>C		intron_variant		ENST00000355243.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX2	ENST00000355243.8	c.411-3248A>C		intron_variant		1	NM_000278.5	P4

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

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.00429

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.197

Alfa AF: 0.211 Hom.: 1635

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11190698; hg19: chr10-102536007;