10-100745602-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_000278.5(PAX2):c.-659C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 238,814 control chromosomes in the GnomAD database, including 76,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (48638 hom., cov: 31)
  • Exomes 𝑓: 0.80 (28141 hom.)
• Consequence: PAX2 NM_000278.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0270

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=-0.29).
• BP6: Variant 10-100745602-C-A is Benign according to our data. Variant chr10-100745602-C-A is described in ClinVar as [Benign]. Clinvar id is 1245518.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
PAX2	NM_000278.5	c.-659C>A		5_prime_UTR_variant	1/10	ENST00000355243.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX2	ENST00000355243.8	c.-659C>A		5_prime_UTR_variant	1/10	1	NM_000278.5	P4

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121171 AN: 151812 Hom.: 48595 Cov.: 31

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.778

GnomAD4 exome AF: 0.802 AC: 69731 AN: 86894 Hom.: 28141 AF XY: 0.804 AC XY: 33119 AN XY: 41182

Gnomad4 AFR exome AF: 0.712

Gnomad4 AMR exome AF: 0.805

Gnomad4 ASJ exome AF: 0.776

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.928

Gnomad4 FIN exome AF: 0.810

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.803

GnomAD4 genome AF: 0.798 AC: 121265 AN: 151920 Hom.: 48638 Cov.: 31 AF XY: 0.806 AC XY: 59875 AN XY: 74248

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.781

Alfa AF: 0.801 Hom.: 6070

Bravo AF: 0.790

Asia WGS AF: 0.945 AC: 3259 AN: 3450

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	15
Dann	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4523631; hg19: chr10-102505359;