10-100745390-A-T

Position:

• chr10-100745390-A-T

Variant summary

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

The NM_001304569.2(PAX2):​c.26-803A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 149,672 control chromosomes in the GnomAD database, including 48,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.81 (48517 hom., cov: 25)
• Consequence: PAX2 NM_001304569.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0420

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 10-100745390-A-T is Benign according to our data. Variant chr10-100745390-A-T is described in ClinVar as [Benign]. Clinvar id is 1277635.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	Protein	UniProt
PAX2	NM_001304569.2	c.26-803A>T		intron_variant			NP_001291498.1
PAX2	NM_001374303.1	c.26-803A>T		intron_variant			NP_001361232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000707078.1	c.26-803A>T		intron_variant				ENSP00000516729.1
PAX2	ENST00000679374.1	c.26-4356A>T		intron_variant				ENSP00000506041.1
PAX2	ENST00000553492.5	n.131+9657A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.806 AC: 120548 AN: 149558 Hom.: 48473 Cov.: 25

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.805

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.782

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.806 AC: 120644 AN: 149672 Hom.: 48517 Cov.: 25 AF XY: 0.814 AC XY: 59489 AN XY: 73056

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.922

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.785

Alfa AF: 0.801 Hom.: 5741

Bravo AF: 0.793

Asia WGS AF: 0.946 AC: 3271 AN: 3462

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

Jul 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4341467; hg19: chr10-102505147;