rs192879693
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The ENST00000305737.6(TET2):c.3424T>A(p.Cys1142Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,614,100 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000305737.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TET2 | NM_001127208.3 | c.3409+15T>A | intron_variant | ENST00000380013.9 | |||
TET2-AS1 | NR_126420.1 | n.319-59694A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TET2 | ENST00000380013.9 | c.3409+15T>A | intron_variant | 5 | NM_001127208.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000160 AC: 40AN: 250144Hom.: 1 AF XY: 0.000118 AC XY: 16AN XY: 135518
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461798Hom.: 1 Cov.: 34 AF XY: 0.0000413 AC XY: 30AN XY: 727204
GnomAD4 genome ? AF: 0.000309 AC: 47AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31AN XY: 74490
ClinVar
Submissions by phenotype
TET2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 22, 2023 | The TET2 c.3424T>A variant is predicted to result in the amino acid substitution p.Cys1142Ser. This variant was observed in a healthy cohort in a study of variants in cancer-susceptibility genes (Table S1, Bodian et al. 2014. PubMed ID: 24728327). This variant is listed as likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/135329/). This variant is intronic in an alternative transcript (NM_001127208:c.3409+15T>A). This variant is reported in 0.12% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-106158523-T-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at