10-100745886-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000278.5(PAX2):c.-375C>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 1,092,896 control chromosomes in the GnomAD database, including 350,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (48403 hom., cov: 28)
  • Exomes 𝑓: 0.80 (302383 hom.)
• Consequence: PAX2 NM_000278.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.589

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-100745886-C-A is Benign according to our data. Variant chr10-100745886-C-A is described in ClinVar as [Benign]. Clinvar id is 1175431.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.-375C>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.-375C>A		5_prime_UTR_variant	1/10	1	NM_000278.5	P4

Frequencies

GnomAD3 genomes AF: 0.798 AC: 120638 AN: 151154 Hom.: 48361 Cov.: 28

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.795

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.778

GnomAD4 exome AF: 0.800 AC: 753334 AN: 941636 Hom.: 302383 Cov.: 29 AF XY: 0.800 AC XY: 350095 AN XY: 437866

Gnomad4 AFR exome AF: 0.732

Gnomad4 AMR exome AF: 0.821

Gnomad4 ASJ exome AF: 0.787

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.918

Gnomad4 FIN exome AF: 0.828

Gnomad4 NFE exome AF: 0.795

Gnomad4 OTH exome AF: 0.806

GnomAD4 genome AF: 0.798 AC: 120730 AN: 151260 Hom.: 48403 Cov.: 28 AF XY: 0.806 AC XY: 59571 AN XY: 73882

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.781

Alfa AF: 0.797 Hom.: 6942

Bravo AF: 0.790

Asia WGS AF: 0.947 AC: 3264 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	-0.83
Cadd	Benign	13
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7094977; hg19: chr10-102505643;