2-222244072-C-G

Position:

• chr2-222244072-C-G

Variant summary

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

The NM_181458.4(PAX3):​c.587-11789G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,046 control chromosomes in the GnomAD database, including 20,173 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 0.50 (20173 hom., cov: 32)
• Consequence: PAX3 NM_181458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX3	NM_181458.4	c.587-11789G>C		intron_variant		ENST00000392070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX3	ENST00000392070.7	c.587-11789G>C		intron_variant		1	NM_181458.4	A1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76532 AN: 151928 Hom.: 20154 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.504 AC: 76580 AN: 152046 Hom.: 20173 Cov.: 32 AF XY: 0.507 AC XY: 37720 AN XY: 74328

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.506

Alfa AF: 0.398 Hom.: 1146

Bravo AF: 0.493

Asia WGS AF: 0.541 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.42

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: rs1367414; hg19: chr2-223108791;