rs1800897

Variant names:

• chr10-100809115-C-T
• rs1800897
• NM_000278.5:c.798C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-100809115-C-T
• chr10-100809115-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000278.5(PAX2):​c.798C>T​(p.Asn266Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 1,611,838 control chromosomes in the GnomAD database, including 6,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2438 hom., cov: 32)
  • Exomes 𝑓: 0.051 (3984 hom.)
• Consequence: PAX2 NM_000278.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -0.215
• Publications: 12 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 10-100809115-C-T is Benign according to our data. Variant chr10-100809115-C-T is described in ClinVar as Benign. ClinVar VariationId is 156298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.215 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 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.798C>T	p.Asn266Asn	synonymous	Exon 7 of 10	NP_000269.3
	PAX2	NM_003990.5		c.867C>T	p.Asn289Asn	synonymous	Exon 8 of 11	NP_003981.3
	PAX2	NM_001304569.2		c.891C>T	p.Asn297Asn	synonymous	Exon 8 of 11	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.798C>T	p.Asn266Asn	synonymous	Exon 7 of 10	ENSP00000347385.3	Q02962-3
	PAX2	ENST00000370296.6	TSL:1	c.798C>T	p.Asn266Asn	synonymous	Exon 7 of 11	ENSP00000359319.3	Q02962-4
	PAX2	ENST00000554172.2	TSL:1	c.786C>T	p.Asn262Asn	synonymous	Exon 6 of 7	ENSP00000452489.2	G3V5S4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18930 AN: 151972 Hom.: 2432 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0951

GnomAD2 exomes AF: 0.0744 AC: 18703 AN: 251364 AF XY: 0.0706

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.0697

Gnomad ASJ exome AF: 0.0217

Gnomad EAS exome AF: 0.0975

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.0397

Gnomad OTH exome AF: 0.0534

GnomAD4 exome AF: 0.0515 AC: 75169 AN: 1459748 Hom.: 3984 Cov.: 31 AF XY: 0.0522 AC XY: 37890 AN XY: 726358

African (AFR) AF: 0.346 AC: 11516 AN: 33324

American (AMR) AF: 0.0667 AC: 2983 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0227 AC: 592 AN: 26124

East Asian (EAS) AF: 0.0993 AC: 3938 AN: 39660

South Asian (SAS) AF: 0.110 AC: 9518 AN: 86192

European-Finnish (FIN) AF: 0.0254 AC: 1355 AN: 53340

Middle Eastern (MID) AF: 0.0805 AC: 464 AN: 5764

European-Non Finnish (NFE) AF: 0.0367 AC: 40756 AN: 1110318

Other (OTH) AF: 0.0671 AC: 4047 AN: 60312

GnomAD4 genome AF: 0.125 AC: 18975 AN: 152090 Hom.: 2438 Cov.: 32 AF XY: 0.124 AC XY: 9200 AN XY: 74348

African (AFR) AF: 0.329 AC: 13621 AN: 41416

American (AMR) AF: 0.0694 AC: 1061 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3466

East Asian (EAS) AF: 0.0903 AC: 466 AN: 5162

South Asian (SAS) AF: 0.108 AC: 521 AN: 4820

European-Finnish (FIN) AF: 0.0273 AC: 289 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0381 AC: 2591 AN: 68012

Other (OTH) AF: 0.0989 AC: 209 AN: 2114

Alfa AF: 0.0751 Hom.: 3286

Bravo AF: 0.137

Asia WGS AF: 0.146 AC: 510 AN: 3478

EpiCase AF: 0.0412

EpiControl AF: 0.0372

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (3)
-	-	2	Renal coloboma syndrome;C4014925:Focal segmental glomerulosclerosis 7 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1800897; hg19: chr10-102568872; COSMIC: COSV62292931; COSMIC: COSV62292931;