2-222273318-C-T

Position:

• chr2-222273318-C-T

Variant summary

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

The ENST00000392070.7(PAX3):​c.586+20849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,060 control chromosomes in the GnomAD database, including 4,028 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 0.21 (4028 hom., cov: 33)
• Consequence: PAX3 ENST00000392070.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

Genes affected

PAX3 (HGNC:8617): (paired box 3) This gene is a member of the paired box (PAX) family of transcription factors. Members of the PAX family typically contain a paired box domain and a paired-type homeodomain. These genes play critical roles during fetal development. Mutations in paired box gene 3 are associated with Waardenburg syndrome, craniofacial-deafness-hand syndrome, and alveolar rhabdomyosarcoma. The translocation t(2;13)(q35;q14), which represents a fusion between PAX3 and the forkhead gene, is a frequent finding in alveolar rhabdomyosarcoma. Alternative splicing results in transcripts encoding isoforms with different C-termini. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX3	NM_181458.4	c.586+20849G>A		intron_variant		ENST00000392070.7	NP_852123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX3	ENST00000392070.7	c.586+20849G>A		intron_variant		1	NM_181458.4	ENSP00000375922	A1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32618 AN: 151944 Hom.: 4018 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.215 AC: 32641 AN: 152060 Hom.: 4028 Cov.: 33 AF XY: 0.220 AC XY: 16341 AN XY: 74334

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.221

Alfa AF: 0.102 Hom.: 145

Bravo AF: 0.222

Asia WGS AF: 0.357 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.038
DANN	Benign	0.72

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: rs1367408; hg19: chr2-223138037;