10-100745582-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_000278.5(PAX2):c.-679A>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 0.00897 in 193,014 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (44 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (1 hom.)
• Consequence: PAX2 NM_000278.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.54

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=-0.36).
• BP6: Variant 10-100745582-A-G is Benign according to our data. Variant chr10-100745582-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1190550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1696/151766) while in subpopulation AFR AF= 0.0399 (1648/41278). AF 95% confidence interval is 0.0383. There are 44 homozygotes in gnomad4. There are 746 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1698 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX2	NM_000278.5	c.-679A>G		5_prime_UTR_variant	1/10	ENST00000355243.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX2	ENST00000355243.8	c.-679A>G		5_prime_UTR_variant	1/10	1	NM_000278.5	P4

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1698 AN: 151658 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00575

GnomAD4 exome AF: 0.000849 AC: 35 AN: 41248 Hom.: 1 AF XY: 0.000978 AC XY: 19 AN XY: 19418

Gnomad4 AFR exome AF: 0.0302

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.0112 AC: 1696 AN: 151766 Hom.: 44 Cov.: 32 AF XY: 0.0101 AC XY: 746 AN XY: 74186

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00950 Hom.: 3

Bravo AF: 0.0128

Asia WGS AF: 0.00231 AC: 8 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	21
Dann	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs567740980; hg19: chr10-102505339;