10-100748820-T-G

Variant names:

• chr10-100748820-T-G
• rs4244341
• NM_000278.5:c.44-926T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.85).
• 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 rank	MANE	Protein	UniProt
PAX2	NM_000278.5	c.44-926T>G		intron_variant	Intron 1 of 9	ENST00000355243.8	NP_000269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000355243.8	c.44-926T>G		intron_variant	Intron 1 of 9	1	NM_000278.5	ENSP00000347385.3

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

African (AFR) AF: 0.556 AC: 8779 AN: 15786

American (AMR) AF: 0.831 AC: 819 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 3766 AN: 5152

East Asian (EAS) AF: 0.892 AC: 3244 AN: 3636

South Asian (SAS) AF: 0.794 AC: 13065 AN: 16460

European-Finnish (FIN) AF: 0.888 AC: 245 AN: 276

Middle Eastern (MID) AF: 0.735 AC: 1190 AN: 1620

European-Non Finnish (NFE) AF: 0.783 AC: 596904 AN: 761950

Other (OTH) AF: 0.774 AC: 21119 AN: 27302

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

African (AFR) AF: 0.579 AC: 24002 AN: 41460

American (AMR) AF: 0.790 AC: 12084 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2544 AN: 3470

East Asian (EAS) AF: 0.898 AC: 4623 AN: 5148

South Asian (SAS) AF: 0.788 AC: 3790 AN: 4812

European-Finnish (FIN) AF: 0.865 AC: 9176 AN: 10606

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53242 AN: 67966

Other (OTH) AF: 0.722 AC: 1524 AN: 2112

Alfa AF: 0.770 Hom.: 79508

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
PhyloP100		-0.36
PromoterAI		0.011	Neutral
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: rs4244341; hg19: chr10-102508577;