2-113275190-T-C

Variant names:

• chr2-113275190-T-C
• rs4848323
• NM_003466.4:c.25+3180A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003466.4(PAX8):​c.25+3180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,020 control chromosomes in the GnomAD database, including 24,643 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 0.57 (24643 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PAX8 NM_003466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX8	NM_003466.4	c.25+3180A>G		intron_variant	Intron 2 of 11	ENST00000429538.8	NP_003457.1
PAX8	NM_013952.4	c.25+3180A>G		intron_variant	Intron 2 of 11		NP_039246.1
PAX8	NM_013953.4	c.25+3180A>G		intron_variant	Intron 2 of 9		NP_039247.1
PAX8	NM_013992.4	c.25+3180A>G		intron_variant	Intron 2 of 8		NP_054698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX8	ENST00000429538.8	c.25+3180A>G		intron_variant	Intron 2 of 11	1	NM_003466.4	ENSP00000395498.3

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86187 AN: 151902 Hom.: 24630 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.588

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.567 AC: 86242 AN: 152020 Hom.: 24643 Cov.: 32 AF XY: 0.565 AC XY: 41998 AN XY: 74288

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.587

Alfa AF: 0.580 Hom.: 43006

Bravo AF: 0.577

Asia WGS AF: 0.630 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.85

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: rs4848323; hg19: chr2-114032767;