2-113265640-G-A

Position:

• chr2-113265640-G-A

Variant summary

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

The NM_003466.4(PAX8):​c.25+12730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,922 control chromosomes in the GnomAD database, including 11,759 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 0.39 (11752 hom., cov: 31)
  • Exomes 𝑓: 0.46 (7 hom.)
• Consequence: PAX8 NM_003466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377

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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX8	NM_003466.4	c.25+12730C>T		intron_variant		ENST00000429538.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX8	ENST00000429538.8	c.25+12730C>T		intron_variant		1	NM_003466.4	P1
PAX8-AS1	ENST00000422956.6	n.858G>A		non_coding_transcript_exon_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59072 AN: 151758 Hom.: 11742 Cov.: 31

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.457 AC: 21 AN: 46 Hom.: 7 Cov.: 0 AF XY: 0.321 AC XY: 9 AN XY: 28

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.389 AC: 59114 AN: 151876 Hom.: 11752 Cov.: 31 AF XY: 0.386 AC XY: 28675 AN XY: 74232

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.382

Alfa AF: 0.390 Hom.: 11473

Bravo AF: 0.385

Asia WGS AF: 0.249 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.2
DANN	Benign	0.82

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: rs895415; hg19: chr2-114023217;