4-105233833-TATAGATAG-T

Position:

• chr4-105233833-TATAGATAG-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001127208.3(TET2):​c.-46-46_-46-39del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 794,828 control chromosomes in the GnomAD database, including 91,904 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14250 hom., cov: 0)
  • Exomes 𝑓: 0.48 (77654 hom.)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.131

Genes affected

TET2 (HGNC:25941): (tet methylcytosine dioxygenase 2) The protein encoded by this gene is a methylcytosine dioxygenase that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. The encoded protein is involved in myelopoiesis, and defects in this gene have been associated with several myeloproliferative disorders. Two variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

TET2-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 4-105233833-TATAGATAG-T is Benign according to our data. Variant chr4-105233833-TATAGATAG-T is described in ClinVar as [Benign]. Clinvar id is 1234506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET2	NM_001127208.3	c.-46-46_-46-39del		intron_variant		ENST00000380013.9
TET2-AS1	NR_126420.1	n.319-56169_319-56162del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET2	ENST00000380013.9	c.-46-46_-46-39del		intron_variant		5	NM_001127208.3	A2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64120 AN: 151052 Hom.: 14251 Cov.: 0

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.481 AC: 309780 AN: 643658 Hom.: 77654 AF XY: 0.477 AC XY: 157070 AN XY: 329536

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.460

GnomAD4 genome AF: 0.424 AC: 64126 AN: 151170 Hom.: 14250 Cov.: 0 AF XY: 0.416 AC XY: 30751 AN XY: 73878

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.412

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs58201766; hg19: chr4-106154990;