rs2073244

Variant names:

• chr14-36660669-A-G
• rs2073244
• NM_006194.4:c.-393-1028A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-36660669-A-G
• chr14-36660669-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006194.4(PAX9):​c.-393-1028A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,084 control chromosomes in the GnomAD database, including 8,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8633 hom., cov: 33)
• Consequence: PAX9 NM_006194.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.987
• Publications: 9 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

ENSG00000258661 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-36660669-A-G is Benign according to our data. Variant chr14-36660669-A-G is described in ClinVar as Benign. ClinVar VariationId is 1277566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX9	NM_006194.4	c.-393-1028A>G		intron_variant	Intron 1 of 4		NP_006185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX9	ENST00000402703.6	c.-393-1028A>G		intron_variant	Intron 1 of 4	5		ENSP00000384817.2
PAX9	ENST00000555639.2	c.-79-1342A>G		intron_variant	Intron 1 of 2	5		ENSP00000501203.1
PAX9	ENST00000553267.4	n.334-1028A>G		intron_variant	Intron 1 of 1	4
ENSG00000258661	ENST00000729136.1	n.534+184T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50230 AN: 151966 Hom.: 8630 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.330 AC: 50256 AN: 152084 Hom.: 8633 Cov.: 33 AF XY: 0.331 AC XY: 24598 AN XY: 74344

African (AFR) AF: 0.251 AC: 10404 AN: 41490

American (AMR) AF: 0.292 AC: 4461 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1493 AN: 3466

East Asian (EAS) AF: 0.452 AC: 2334 AN: 5164

South Asian (SAS) AF: 0.415 AC: 2002 AN: 4826

European-Finnish (FIN) AF: 0.310 AC: 3275 AN: 10568

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25028 AN: 67970

Other (OTH) AF: 0.363 AC: 765 AN: 2110

Alfa AF: 0.346 Hom.: 3086

Bravo AF: 0.325

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.32
PhyloP100		0.99
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: rs2073244; hg19: chr14-37129874;