2-222231990-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_181458.4(PAX3):c.792+88C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,208,638 control chromosomes in the GnomAD database, including 395,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (46463 hom., cov: 32)
  • Exomes 𝑓: 0.80 (348616 hom.)
• Consequence: PAX3 NM_181458.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 2-222231990-G-C is Benign according to our data. Variant chr2-222231990-G-C is described in ClinVar as [Benign]. Clinvar id is 1278226.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX3	NM_181458.4	c.792+88C>G		intron_variant		ENST00000392070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX3	ENST00000392070.7	c.792+88C>G		intron_variant		1	NM_181458.4	A1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117741 AN: 152016 Hom.: 46449 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.775

GnomAD4 exome AF: 0.804 AC: 849519 AN: 1056504 Hom.: 348616 AF XY: 0.800 AC XY: 434976 AN XY: 544048

Gnomad4 AFR exome AF: 0.709

Gnomad4 AMR exome AF: 0.737

Gnomad4 ASJ exome AF: 0.776

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.662

Gnomad4 FIN exome AF: 0.826

Gnomad4 NFE exome AF: 0.851

Gnomad4 OTH exome AF: 0.792

GnomAD4 genome AF: 0.774 AC: 117805 AN: 152134 Hom.: 46463 Cov.: 32 AF XY: 0.768 AC XY: 57095 AN XY: 74382

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.775

Alfa AF: 0.765 Hom.: 2426

Bravo AF: 0.768

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

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.067
Dann	Benign	0.35

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: rs1965791; hg19: chr2-223096709; COSMIC: COSV60588973;