2-222201298-A-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181458.4(PAX3):c.*109_*110insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 1,595,896 control chromosomes in the GnomAD database, including 11,430 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2521 hom., cov: 29)
  • Exomes 𝑓: 0.082 (8909 hom.)
• Consequence: PAX3 NM_181458.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 -10 ACMG points.

• BP6: Variant 2-222201298-A-AC is Benign according to our data. Variant chr2-222201298-A-AC is described in ClinVar as [Benign]. Clinvar id is 1264428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX3	NM_181458.4	c.*109_*110insG		3_prime_UTR_variant	9/9	ENST00000392070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX3	ENST00000392070.7	c.*109_*110insG		3_prime_UTR_variant	9/9	1	NM_181458.4	A1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21237 AN: 147866 Hom.: 2520 Cov.: 29

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0962

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.0819 AC: 118563 AN: 1447932 Hom.: 8909 Cov.: 34 AF XY: 0.0848 AC XY: 61135 AN XY: 720522

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.556

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.0435

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.144 AC: 21277 AN: 147964 Hom.: 2521 Cov.: 29 AF XY: 0.152 AC XY: 10942 AN XY: 71938

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0493

Gnomad4 OTH AF: 0.147

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

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs3832105; hg19: chr2-223066017;