10-100748820-T-G

Position:

• chr10-100748820-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000278.5(PAX2):​c.44-926T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 985,240 control chromosomes in the GnomAD database, including 295,377 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 0.74 (42110 hom., cov: 31)
  • Exomes 𝑓: 0.78 (253267 hom.)
• Consequence: PAX2 NM_000278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX2	NM_000278.5	c.44-926T>G		intron_variant		ENST00000355243.8	NP_000269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000355243.8	c.44-926T>G		intron_variant		1	NM_000278.5	ENSP00000347385	P4

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111924 AN: 151954 Hom.: 42087 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.779 AC: 649131 AN: 833168 Hom.: 253267 Cov.: 48 AF XY: 0.778 AC XY: 299472 AN XY: 384758

Gnomad4 AFR exome AF: 0.556

Gnomad4 AMR exome AF: 0.831

Gnomad4 ASJ exome AF: 0.731

Gnomad4 EAS exome AF: 0.892

Gnomad4 SAS exome AF: 0.794

Gnomad4 FIN exome AF: 0.888

Gnomad4 NFE exome AF: 0.783

Gnomad4 OTH exome AF: 0.774

GnomAD4 genome AF: 0.736 AC: 111997 AN: 152072 Hom.: 42110 Cov.: 31 AF XY: 0.746 AC XY: 55431 AN XY: 74330

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.722

Alfa AF: 0.772 Hom.: 54142

Bravo AF: 0.724

Asia WGS AF: 0.788 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.34

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: rs4244341; hg19: chr10-102508577;