2-113243289-A-G

Position:

• chr2-113243289-A-G

Variant summary

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

The NM_003466.4(PAX8):​c.390-511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,090 control chromosomes in the GnomAD database, including 18,524 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 0.49 (18524 hom., cov: 33)
• Consequence: PAX8 NM_003466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

Genes affected

PAX8 (HGNC:8622): (paired box 8) This gene encodes a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins that contain a paired box domain, an octapeptide, and a paired-type homeodomain. This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. Mutations in this gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas and atypical follicular thyroid adenomas. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

PAX8-AS1 (HGNC:49271): (PAX8 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX8	NM_003466.4	c.390-511T>C		intron_variant		ENST00000429538.8	NP_003457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX8	ENST00000429538.8	c.390-511T>C		intron_variant		1	NM_003466.4	ENSP00000395498	P1
PAX8-AS1	ENST00000422956.6	n.35+7719A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74112 AN: 151970 Hom.: 18506 Cov.: 33

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.488 AC: 74189 AN: 152090 Hom.: 18524 Cov.: 33 AF XY: 0.490 AC XY: 36467 AN XY: 74354

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.466

Alfa AF: 0.449 Hom.: 20694

Bravo AF: 0.481

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.55
DANN	Benign	0.51

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: rs2863244; hg19: chr2-114000866;