chr2-113263271-T-G

Variant names:

• chr2-113263271-T-G
• rs1466018
• NM_003466.4:c.25+15099A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003466.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX8	NM_003466.4	MANE Select	c.25+15099A>C		intron	N/A	NP_003457.1
	PAX8	NM_013952.4		c.25+15099A>C		intron	N/A	NP_039246.1
	PAX8	NM_013953.4		c.25+15099A>C		intron	N/A	NP_039247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX8	ENST00000429538.8	TSL:1 MANE Select	c.25+15099A>C		intron	N/A	ENSP00000395498.3
	PAX8	ENST00000263334.9	TSL:1	c.25+15099A>C		intron	N/A	ENSP00000263334.6
	PAX8	ENST00000348715.9	TSL:1	c.25+15099A>C		intron	N/A	ENSP00000314750.5

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.529 AC: 164 AN: 310

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.650 AC: 26 AN: 40

Other (OTH) AF: 0.667 AC: 8 AN: 12

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

African (AFR) AF: 0.336 AC: 13931 AN: 41472

American (AMR) AF: 0.555 AC: 8496 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2007 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3660 AN: 5180

South Asian (SAS) AF: 0.508 AC: 2449 AN: 4824

European-Finnish (FIN) AF: 0.454 AC: 4792 AN: 10562

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36281 AN: 67968

Other (OTH) AF: 0.510 AC: 1074 AN: 2106

Alfa AF: 0.524 Hom.: 22967

Bravo AF: 0.486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		-0.56
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: rs1466018; hg19: chr2-114020848;