10-100746101-G-T

Position:

• chr10-100746101-G-T

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.-160G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,543,896 control chromosomes in the GnomAD database, including 1,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (135 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1459 hom.)
• Consequence: PAX2 NM_000278.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.93

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=-0.82).
• BP6: Variant 10-100746101-G-T is Benign according to our data. Variant chr10-100746101-G-T is described in ClinVar as [Benign]. Clinvar id is 1256887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-100746101-G-T is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX2	NM_000278.5	c.-160G>T		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.-160G>T		5_prime_UTR_variant	1/10	1	NM_000278.5	ENSP00000347385	P4

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5381 AN: 150724 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0624

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00824

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.0795

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0498

GnomAD4 exome AF: 0.0428 AC: 59639 AN: 1393050 Hom.: 1459 Cov.: 30 AF XY: 0.0421 AC XY: 29025 AN XY: 688822

Gnomad4 AFR exome AF: 0.0103

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.0549

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00836

Gnomad4 FIN exome AF: 0.0476

Gnomad4 NFE exome AF: 0.0475

Gnomad4 OTH exome AF: 0.0428

GnomAD4 genome AF: 0.0357 AC: 5382 AN: 150846 Hom.: 135 Cov.: 32 AF XY: 0.0357 AC XY: 2635 AN XY: 73730

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.0447

Gnomad4 ASJ AF: 0.0624

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00824

Gnomad4 FIN AF: 0.0572

Gnomad4 NFE AF: 0.0482

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.00924 Hom.: 4

Bravo AF: 0.0339

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs148125352; hg19: chr10-102505858;