10-100805712-C-T

Variant names:

• chr10-100805712-C-T
• rs2077642
• NM_000278.5:c.617-718C>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.617-718C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,078 control chromosomes in the GnomAD database, including 23,883 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 0.51 (23883 hom., cov: 32)
• Consequence: PAX2 NM_000278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 4 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, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• 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 = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000278.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX2	NM_000278.5	MANE Select	c.617-718C>T		intron	N/A	NP_000269.3
	PAX2	NM_003990.5		c.686-718C>T		intron	N/A	NP_003981.3
	PAX2	NM_001304569.2		c.710-718C>T		intron	N/A	NP_001291498.1	A0A9L9PYK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX2	ENST00000355243.8	TSL:1 MANE Select	c.617-718C>T		intron	N/A	ENSP00000347385.3	Q02962-3
	PAX2	ENST00000370296.6	TSL:1	c.617-718C>T		intron	N/A	ENSP00000359319.3	Q02962-4
	PAX2	ENST00000554172.2	TSL:1	c.605-718C>T		intron	N/A	ENSP00000452489.2	G3V5S4

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77967 AN: 151960 Hom.: 23880 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.513 AC: 77990 AN: 152078 Hom.: 23883 Cov.: 32 AF XY: 0.528 AC XY: 39218 AN XY: 74324

African (AFR) AF: 0.168 AC: 6991 AN: 41492

American (AMR) AF: 0.635 AC: 9718 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2291 AN: 3470

East Asian (EAS) AF: 0.906 AC: 4669 AN: 5156

South Asian (SAS) AF: 0.665 AC: 3207 AN: 4822

European-Finnish (FIN) AF: 0.752 AC: 7959 AN: 10584

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41313 AN: 67940

Other (OTH) AF: 0.545 AC: 1150 AN: 2110

Alfa AF: 0.585 Hom.: 14718

Bravo AF: 0.489

Asia WGS AF: 0.728 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.41
PhyloP100		-0.28
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: rs2077642; hg19: chr10-102565469;