2-113263271-T-G

Position:

• chr2-113263271-T-G

Variant summary

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

The NM_003466.4(PAX8):​c.25+15099A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,458 control chromosomes in the GnomAD database, including 18,391 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 0.48 (18335 hom., cov: 33)
  • Exomes 𝑓: 0.56 (56 hom.)
• Consequence: PAX8 NM_003466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX8	NM_003466.4	c.25+15099A>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.25+15099A>C		intron_variant		1	NM_003466.4	ENSP00000395498.3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73266 AN: 151968 Hom.: 18338 Cov.: 33

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.559 AC: 208 AN: 372 Hom.: 56 Cov.: 0 AF XY: 0.542 AC XY: 129 AN XY: 238

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.650

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.482 AC: 73287 AN: 152086 Hom.: 18335 Cov.: 33 AF XY: 0.480 AC XY: 35730 AN XY: 74360

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.510

Alfa AF: 0.523 Hom.: 16113

Bravo AF: 0.486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.43

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: rs1466018; hg19: chr2-114020848;