10-100746058-A-G

Position:

• chr10-100746058-A-G

Variant summary

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

The NM_000278.5(PAX2):​c.-203A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,466,716 control chromosomes in the GnomAD database, including 480,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48831 hom., cov: 30)
  • Exomes 𝑓: 0.81 (432058 hom.)
• Consequence: PAX2 NM_000278.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.404

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=-0.84).
• BP6: Variant 10-100746058-A-G is Benign according to our data. Variant chr10-100746058-A-G is described in ClinVar as [Benign]. Clinvar id is 1250881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-100746058-A-G is described in Lovd as [Benign].
• 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	Protein	UniProt
PAX2	NM_000278.5	c.-203A>G		5_prime_UTR_variant	1/10	ENST00000355243.8	NP_000269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000355243.8	c.-203A>G		5_prime_UTR_variant	1/10	1	NM_000278.5	ENSP00000347385	P4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121344 AN: 151530 Hom.: 48787 Cov.: 30

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.778

GnomAD4 exome AF: 0.809 AC: 1064063 AN: 1315074 Hom.: 432058 Cov.: 28 AF XY: 0.811 AC XY: 522243 AN XY: 643822

Gnomad4 AFR exome AF: 0.741

Gnomad4 AMR exome AF: 0.842

Gnomad4 ASJ exome AF: 0.789

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.920

Gnomad4 FIN exome AF: 0.850

Gnomad4 NFE exome AF: 0.796

Gnomad4 OTH exome AF: 0.811

GnomAD4 genome AF: 0.801 AC: 121441 AN: 151642 Hom.: 48831 Cov.: 30 AF XY: 0.809 AC XY: 59960 AN XY: 74108

Gnomad4 AFR AF: 0.755

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: 0.781

Alfa AF: 0.797 Hom.: 9720

Bravo AF: 0.793

Asia WGS AF: 0.946 AC: 3283 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.4
DANN	Benign	0.42

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: rs11190680; hg19: chr10-102505815;