2-113253214-C-T

Variant names:

• chr2-113253214-C-T
• rs4848320
• NM_003466.4:c.26-6295G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003466.4(PAX8):​c.26-6295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,106 control chromosomes in the GnomAD database, including 3,848 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 0.21 (3848 hom., cov: 32)
• Consequence: PAX8 NM_003466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 29 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX8	NM_003466.4	c.26-6295G>A		intron_variant	Intron 2 of 11	ENST00000429538.8	NP_003457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX8	ENST00000429538.8	c.26-6295G>A		intron_variant	Intron 2 of 11	1	NM_003466.4	ENSP00000395498.3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32068 AN: 151988 Hom.: 3846 Cov.: 32

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.211 AC: 32087 AN: 152106 Hom.: 3848 Cov.: 32 AF XY: 0.214 AC XY: 15936 AN XY: 74346

African (AFR) AF: 0.0883 AC: 3666 AN: 41510

American (AMR) AF: 0.216 AC: 3303 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3470

East Asian (EAS) AF: 0.186 AC: 962 AN: 5174

South Asian (SAS) AF: 0.354 AC: 1707 AN: 4828

European-Finnish (FIN) AF: 0.306 AC: 3227 AN: 10548

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17816 AN: 67976

Other (OTH) AF: 0.219 AC: 462 AN: 2110

Alfa AF: 0.241 Hom.: 8087

Bravo AF: 0.197

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.44
PhyloP100		-0.35
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: rs4848320; hg19: chr2-114010791;