Variant chr10-100745847-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_000278.5(PAX2):c.-414C>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 0.00992 in 1,126,854 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 6 hom., cov: 33)

Exomes 𝑓: 0.011 ( 51 hom. )

Consequence

PAX2
NM_000278.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.133

Variant links:

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]

PAX2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 10-100745847-C-T is Benign according to our data. Variant chr10-100745847-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1210888.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00613 (934/152276) while in subpopulation NFE AF= 0.0094 (639/67996). AF 95% confidence interval is 0.00879. There are 6 homozygotes in gnomad4. There are 463 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 934 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX2	NM_000278.5 linkuse as main transcript	c.-414C>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 linkuse as main transcript	c.-414C>T		5_prime_UTR_variant	1/10	1	NM_000278.5	ENSP00000347385	P4	Q02962-3

Frequencies

GnomAD3 genomes

AF:

0.00614

AC:

935

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00940

Gnomad OTH

AF:

0.00526

GnomAD4 exome

AF:

0.0105

AC:

10241

AN:

974578

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

4644

AN XY:

454306

show subpopulations

Gnomad4 AFR exome

AF:

0.00109

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00164

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000381

Gnomad4 FIN exome

AF:

0.00937

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00892

GnomAD4 genome

AF:

0.00613

AC:

934

AN:

152276

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

463

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.00940

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00454

Hom.:

Bravo

AF:

0.00538

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.96

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over