chr2-222210549-C-T

Position:

• chr2-222210549-C-T

Variant summary

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

The NM_181458.4(PAX3):​c.1174-8359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,056 control chromosomes in the GnomAD database, including 8,682 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 0.30 (8682 hom., cov: 32)
• Consequence: PAX3 NM_181458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX3	NM_181458.4	c.1174-8359G>A		intron_variant		ENST00000392070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX3	ENST00000392070.7	c.1174-8359G>A		intron_variant		1	NM_181458.4	A1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45707 AN: 151938 Hom.: 8684 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.301 AC: 45705 AN: 152056 Hom.: 8682 Cov.: 32 AF XY: 0.297 AC XY: 22036 AN XY: 74292

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.0897

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.297

Alfa AF: 0.251 Hom.: 708

Bravo AF: 0.276

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.67

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: rs7565552; hg19: chr2-223075268;