10-100735764-A-G

Variant names:

• chr10-100735764-A-G
• rs4919486
• NM_001304569.2:c.25+31A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001304569.2(PAX2):​c.25+31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,027,292 control chromosomes in the GnomAD database, including 329,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (49012 hom., cov: 31)
  • Exomes 𝑓: 0.80 (280970 hom.)
• Consequence: PAX2 NM_001304569.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.70

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-100735764-A-G is Benign according to our data. Variant chr10-100735764-A-G is described in ClinVar as [Benign]. Clinvar id is 1326988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX2	NM_001304569.2	c.25+31A>G		intron_variant	Intron 1 of 10		NP_001291498.1
PAX2	NM_001374303.1	c.25+31A>G		intron_variant	Intron 1 of 2		NP_001361232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000707078.1	c.25+31A>G		intron_variant	Intron 1 of 10			ENSP00000516729.1
PAX2	ENST00000679374.1	c.25+31A>G		intron_variant	Intron 1 of 9			ENSP00000506041.1
PAX2	ENST00000553492.5	n.131+31A>G		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121702 AN: 151862 Hom.: 48964 Cov.: 31

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.777

GnomAD4 exome AF: 0.801 AC: 700696 AN: 875312 Hom.: 280970 Cov.: 23 AF XY: 0.800 AC XY: 323578 AN XY: 404436

Gnomad4 AFR exome AF: 0.742

Gnomad4 AMR exome AF: 0.831

Gnomad4 ASJ exome AF: 0.789

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.923

Gnomad4 FIN exome AF: 0.839

Gnomad4 NFE exome AF: 0.796

Gnomad4 OTH exome AF: 0.807

GnomAD4 genome AF: 0.801 AC: 121806 AN: 151980 Hom.: 49012 Cov.: 31 AF XY: 0.809 AC XY: 60141 AN XY: 74304

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.780

Alfa AF: 0.802 Hom.: 6081

Bravo AF: 0.794

Asia WGS AF: 0.947 AC: 3291 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 90. Only high quality variants are reported. -

Renal coloboma syndrome Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Focal segmental glomerulosclerosis 7 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.036
DANN	Benign	0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4919486; hg19: chr10-102495521;