2-222201298-ACCC-ACC

Variant names:

• chr2-222201298-AC-A
• rs3832105
• NM_181458.4:c.*109delG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_181458.4(PAX3):​c.*109delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000689 in 1,597,586 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: PAX3 NM_181458.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 1 publications found

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]

PAX3 Gene-Disease associations (from GenCC):

• craniofacial-deafness-hand syndrome

  Inheritance: AD, Unknown Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• Waardenburg syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Waardenburg syndrome type 1

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• Waardenburg syndrome type 3

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX3	NM_181458.4	MANE Select	c.*109delG		3_prime_UTR	Exon 9 of 9	NP_852123.1	P23760-7
	PAX3	NM_001127366.3		c.*109delG		3_prime_UTR	Exon 9 of 9	NP_001120838.1	P23760-6
	PAX3	NM_181461.4		c.*105delG		3_prime_UTR	Exon 8 of 8	NP_852126.1	P23760-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX3	ENST00000392070.7	TSL:1 MANE Select	c.*109delG		3_prime_UTR	Exon 9 of 9	ENSP00000375922.3	P23760-7
	PAX3	ENST00000336840.11	TSL:1	c.1205-59delG		intron	N/A	ENSP00000338767.5	P23760-5
	PAX3	ENST00000392069.6	TSL:5	c.1452-59delG		intron	N/A	ENSP00000375921.2	P23760-8

Frequencies

GnomAD3 genomes AF: 0.0000540 AC: 8 AN: 148216 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000675

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000744

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000704 AC: 102 AN: 1449370 Hom.: 0 Cov.: 34 AF XY: 0.0000735 AC XY: 53 AN XY: 721234

African (AFR) AF: 0.0000911 AC: 3 AN: 32938

American (AMR) AF: 0.00 AC: 0 AN: 44174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 35670

South Asian (SAS) AF: 0.0000585 AC: 5 AN: 85502

European-Finnish (FIN) AF: 0.0000379 AC: 2 AN: 52802

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5746

European-Non Finnish (NFE) AF: 0.0000813 AC: 90 AN: 1106818

Other (OTH) AF: 0.0000167 AC: 1 AN: 59748

GnomAD4 genome AF: 0.0000540 AC: 8 AN: 148216 Hom.: 0 Cov.: 29 AF XY: 0.0000416 AC XY: 3 AN XY: 72048

African (AFR) AF: 0.0000502 AC: 2 AN: 39880

American (AMR) AF: 0.0000675 AC: 1 AN: 14818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 4872

South Asian (SAS) AF: 0.00 AC: 0 AN: 4646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000744 AC: 5 AN: 67228

Other (OTH) AF: 0.00 AC: 0 AN: 2030

Alfa AF: 0.0000629 Hom.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3832105; hg19: chr2-223066017; COSMIC: COSV100399257; COSMIC: COSV100399257;