rs2295218

Variant names:

• chr14-36665286-T-A
• rs2295218
• NM_001372076.1:c.632-1176T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372076.1(PAX9):​c.632-1176T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,814 control chromosomes in the GnomAD database, including 8,813 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 0.33 (8813 hom., cov: 32)
• Consequence: PAX9 NM_001372076.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 5 publications found

Genes affected

PAX9 (HGNC:8623): (paired box 9) This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. Mice lacking this gene exhibit impaired development of organs, musculature and the skeleton, including absent and abnormally developed teeth, and neonatal lethality. Mutations in the human gene are associated with selective tooth agenesis-3. [provided by RefSeq, Sep 2015]

PAX9 Gene-Disease associations (from GenCC):

• tooth agenesis, selective, 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX9	NM_001372076.1	c.632-1176T>A		intron_variant	Intron 2 of 3	ENST00000361487.7	NP_001359005.1
PAX9	NM_006194.4	c.632-1176T>A		intron_variant	Intron 3 of 4		NP_006185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX9	ENST00000361487.7	c.632-1176T>A		intron_variant	Intron 2 of 3	1	NM_001372076.1	ENSP00000355245.6
PAX9	ENST00000402703.6	c.632-1176T>A		intron_variant	Intron 3 of 4	5		ENSP00000384817.2
PAX9	ENST00000554201.1	n.951-1176T>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50573 AN: 151696 Hom.: 8810 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.333 AC: 50598 AN: 151814 Hom.: 8813 Cov.: 32 AF XY: 0.334 AC XY: 24765 AN XY: 74182

African (AFR) AF: 0.240 AC: 9951 AN: 41450

American (AMR) AF: 0.294 AC: 4472 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1513 AN: 3458

East Asian (EAS) AF: 0.450 AC: 2327 AN: 5166

South Asian (SAS) AF: 0.419 AC: 2014 AN: 4804

European-Finnish (FIN) AF: 0.326 AC: 3425 AN: 10516

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25629 AN: 67864

Other (OTH) AF: 0.365 AC: 771 AN: 2114

Alfa AF: 0.344 Hom.: 1121

Bravo AF: 0.326

Asia WGS AF: 0.413 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.4
DANN	Benign	0.70
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs2295218; hg19: chr14-37134491;