2-113236840-G-T

Variant names:

• chr2-113236840-G-T
• rs1110839
• NM_003466.4:c.778-119C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003466.4(PAX8):​c.778-119C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,129,780 control chromosomes in the GnomAD database, including 139,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16170 hom., cov: 32)
  • Exomes 𝑓: 0.50 (123811 hom.)
• Consequence: PAX8 NM_003466.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50
• Publications: 34 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-113236840-G-T is Benign according to our data. Variant chr2-113236840-G-T is described in ClinVar as Benign. ClinVar VariationId is 1265957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX8	NM_003466.4	c.778-119C>A		intron_variant	Intron 7 of 11	ENST00000429538.8	NP_003457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX8	ENST00000429538.8	c.778-119C>A		intron_variant	Intron 7 of 11	1	NM_003466.4	ENSP00000395498.3

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68331 AN: 151866 Hom.: 16172 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.490

GnomAD4 exome AF: 0.498 AC: 486471 AN: 977796 Hom.: 123811 Cov.: 12 AF XY: 0.499 AC XY: 241764 AN XY: 484736

African (AFR) AF: 0.297 AC: 6762 AN: 22778

American (AMR) AF: 0.566 AC: 13172 AN: 23280

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 10260 AN: 17554

East Asian (EAS) AF: 0.649 AC: 20569 AN: 31690

South Asian (SAS) AF: 0.521 AC: 29645 AN: 56950

European-Finnish (FIN) AF: 0.414 AC: 12881 AN: 31082

Middle Eastern (MID) AF: 0.537 AC: 2500 AN: 4658

European-Non Finnish (NFE) AF: 0.494 AC: 368823 AN: 746420

Other (OTH) AF: 0.504 AC: 21859 AN: 43384

GnomAD4 genome AF: 0.450 AC: 68359 AN: 151984 Hom.: 16170 Cov.: 32 AF XY: 0.450 AC XY: 33409 AN XY: 74310

African (AFR) AF: 0.304 AC: 12576 AN: 41432

American (AMR) AF: 0.535 AC: 8164 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1937 AN: 3466

East Asian (EAS) AF: 0.652 AC: 3360 AN: 5156

South Asian (SAS) AF: 0.513 AC: 2478 AN: 4826

European-Finnish (FIN) AF: 0.399 AC: 4221 AN: 10570

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34056 AN: 67946

Other (OTH) AF: 0.491 AC: 1036 AN: 2110

Alfa AF: 0.490 Hom.: 30276

Bravo AF: 0.456

Asia WGS AF: 0.529 AC: 1842 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.50
DANN	Benign	0.68
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1110839; hg19: chr2-113994417;