2-222275492-C-A

Position:

• chr2-222275492-C-A

Variant summary

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

The NM_181458.4(PAX3):​c.586+18675G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,264 control chromosomes in the GnomAD database, including 4,024 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 0.22 (4024 hom., cov: 33)
• Consequence: PAX3 NM_181458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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]

PAX3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX3	NM_181458.4	c.586+18675G>T		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+18675G>T		intron_variant		1	NM_181458.4	ENSP00000375922.3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32595 AN: 151178 Hom.: 4014 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.169

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: 0.216 AC: 32618 AN: 151264 Hom.: 4024 Cov.: 33 AF XY: 0.221 AC XY: 16336 AN XY: 73856

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.221

Alfa AF: 0.212 Hom.: 451

Bravo AF: 0.222

Asia WGS AF: 0.354 AC: 1218 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.8
DANN	Benign	0.52

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: rs6734345; hg19: chr2-223140211;