chr10-100747582-C-T

Variant names:

• chr10-100747582-C-T
• rs6421335
• NM_000278.5:c.43+1279C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000278.5(PAX2):​c.43+1279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 980,140 control chromosomes in the GnomAD database, including 297,255 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (47034 hom., cov: 29)
  • Exomes 𝑓: 0.78 (250221 hom.)
• Consequence: PAX2 NM_000278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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=-0.59).
• 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 rank	MANE	Protein	UniProt
PAX2	NM_000278.5	c.43+1279C>T		intron_variant	Intron 1 of 9	ENST00000355243.8	NP_000269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX2	ENST00000355243.8	c.43+1279C>T		intron_variant	Intron 1 of 9	1	NM_000278.5	ENSP00000347385.3

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119083 AN: 151492 Hom.: 46991 Cov.: 29

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.768

GnomAD4 exome AF: 0.776 AC: 643248 AN: 828530 Hom.: 250221 Cov.: 19 AF XY: 0.776 AC XY: 296884 AN XY: 382746

Gnomad4 AFR exome AF: 0.740

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.763

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.921

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.773

Gnomad4 OTH exome AF: 0.791

GnomAD4 genome AF: 0.786 AC: 119184 AN: 151610 Hom.: 47034 Cov.: 29 AF XY: 0.795 AC XY: 58911 AN XY: 74070

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.771

Alfa AF: 0.782 Hom.: 6762

Bravo AF: 0.778

Asia WGS AF: 0.943 AC: 3274 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.88

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: rs6421335; hg19: chr10-102507339;