rs2236007

Variant names:

• chr14-36663564-G-A
• rs2236007
• NM_001372076.1:c.631+41G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-36663564-G-A
• chr14-36663564-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001372076.1(PAX9):​c.631+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,609,186 control chromosomes in the GnomAD database, including 33,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2505 hom., cov: 33)
  • Exomes 𝑓: 0.20 (30834 hom.)
• Consequence: PAX9 NM_001372076.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.243
• Publications: 89 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-36663564-G-A is Benign according to our data. Variant chr14-36663564-G-A is described in ClinVar as Benign. ClinVar VariationId is 225820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372076.1. 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
	PAX9	NM_001372076.1	MANE Select	c.631+41G>A		intron	N/A	NP_001359005.1	P55771
	PAX9	NM_006194.4		c.631+41G>A		intron	N/A	NP_006185.1	P55771

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX9	ENST00000361487.7	TSL:1 MANE Select	c.631+41G>A		intron	N/A	ENSP00000355245.6	P55771
	PAX9	ENST00000402703.6	TSL:5	c.631+41G>A		intron	N/A	ENSP00000384817.2	P55771
	PAX9	ENST00000554201.1	TSL:2	n.950+41G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24906 AN: 152050 Hom.: 2505 Cov.: 33

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.174

GnomAD2 exomes AF: 0.182 AC: 42347 AN: 232420 AF XY: 0.188

Gnomad AFR exome AF: 0.0692

Gnomad AMR exome AF: 0.0950

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.295

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.202 AC: 293902 AN: 1457018 Hom.: 30834 Cov.: 35 AF XY: 0.202 AC XY: 146349 AN XY: 724752

African (AFR) AF: 0.0630 AC: 2105 AN: 33392

American (AMR) AF: 0.101 AC: 4512 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4320 AN: 26090

East Asian (EAS) AF: 0.274 AC: 10832 AN: 39602

South Asian (SAS) AF: 0.170 AC: 14614 AN: 85912

European-Finnish (FIN) AF: 0.172 AC: 8876 AN: 51544

Middle Eastern (MID) AF: 0.200 AC: 1137 AN: 5680

European-Non Finnish (NFE) AF: 0.212 AC: 235713 AN: 1110048

Other (OTH) AF: 0.196 AC: 11793 AN: 60236

GnomAD4 genome AF: 0.164 AC: 24909 AN: 152168 Hom.: 2505 Cov.: 33 AF XY: 0.163 AC XY: 12138 AN XY: 74380

African (AFR) AF: 0.0699 AC: 2905 AN: 41536

American (AMR) AF: 0.133 AC: 2037 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3472

East Asian (EAS) AF: 0.294 AC: 1513 AN: 5142

South Asian (SAS) AF: 0.167 AC: 806 AN: 4814

European-Finnish (FIN) AF: 0.177 AC: 1879 AN: 10606

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14551 AN: 67990

Other (OTH) AF: 0.175 AC: 371 AN: 2114

Alfa AF: 0.185 Hom.: 4411

Bravo AF: 0.159

Asia WGS AF: 0.218 AC: 755 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypodontia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.79
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2236007; hg19: chr14-37132769;