2-113221363-C-G

Position:

• chr2-113221363-C-G

Variant summary

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

The NM_003466.4(PAX8):​c.1190-1185G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,054 control chromosomes in the GnomAD database, including 9,547 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 0.35 (9547 hom., cov: 32)
• Consequence: PAX8 NM_003466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX8	NM_003466.4	c.1190-1185G>C		intron_variant		ENST00000429538.8	NP_003457.1
PAX8	NM_013952.4	c.1111-1185G>C		intron_variant			NP_039246.1
PAX8	NM_013953.4	c.880-1185G>C		intron_variant			NP_039247.1
PAX8	NM_013992.4	c.778-1185G>C		intron_variant			NP_054698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX8	ENST00000429538.8	c.1190-1185G>C		intron_variant		1	NM_003466.4	ENSP00000395498	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53480 AN: 151936 Hom.: 9538 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.352 AC: 53527 AN: 152054 Hom.: 9547 Cov.: 32 AF XY: 0.355 AC XY: 26355 AN XY: 74322

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.355

Alfa AF: 0.340 Hom.: 4822

Bravo AF: 0.341

Asia WGS AF: 0.420 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.7
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs11123170; hg19: chr2-113978940;