2-222201817-CA-C

Position:

• chr2-222201817-CA-C

Variant summary

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

The NM_181458.4(PAX3):​c.1420+126del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,230,762 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 24)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: PAX3 NM_181458.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.474

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 2-222201817-CA-C is Benign according to our data. Variant chr2-222201817-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1216859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX3	NM_181458.4	c.1420+126del		intron_variant		ENST00000392070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX3	ENST00000392070.7	c.1420+126del		intron_variant		1	NM_181458.4	A1

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 410 AN: 127118 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00252

Gnomad ASJ AF: 0.000974

Gnomad EAS AF: 0.00133

Gnomad SAS AF: 0.00369

Gnomad FIN AF: 0.00988

Gnomad MID AF: 0.00368

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.00581

GnomAD4 exome AF: 0.119 AC: 131169 AN: 1103586 Hom.: 0 Cov.: 0 AF XY: 0.121 AC XY: 66288 AN XY: 547914

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.00323 AC: 411 AN: 127176 Hom.: 1 Cov.: 24 AF XY: 0.00344 AC XY: 210 AN XY: 61060

Gnomad4 AFR AF: 0.00526

Gnomad4 AMR AF: 0.00252

Gnomad4 ASJ AF: 0.000974

Gnomad4 EAS AF: 0.00133

Gnomad4 SAS AF: 0.00370

Gnomad4 FIN AF: 0.00988

Gnomad4 NFE AF: 0.00153

Gnomad4 OTH AF: 0.00575

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 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: rs368725878; hg19: chr2-223066536;