chr22-30612895-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000355.4(TCN2):c.280G>A(p.Gly94Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,613,952 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000355.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TCN2 | NM_000355.4 | c.280G>A | p.Gly94Ser | missense_variant | 3/9 | ENST00000215838.8 | NP_000346.2 | |
TCN2 | NM_001184726.2 | c.280G>A | p.Gly94Ser | missense_variant | 3/9 | NP_001171655.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCN2 | ENST00000215838.8 | c.280G>A | p.Gly94Ser | missense_variant | 3/9 | 1 | NM_000355.4 | ENSP00000215838.3 |
Frequencies
GnomAD3 genomes AF: 0.00210 AC: 320AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00212 AC: 533AN: 251304Hom.: 1 AF XY: 0.00205 AC XY: 279AN XY: 135862
GnomAD4 exome AF: 0.00257 AC: 3761AN: 1461644Hom.: 7 Cov.: 32 AF XY: 0.00254 AC XY: 1848AN XY: 727096
GnomAD4 genome AF: 0.00210 AC: 320AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.00200 AC XY: 149AN XY: 74468
ClinVar
Submissions by phenotype
Transcobalamin II deficiency Benign:5
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Jun 02, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 03, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Jul 05, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
not provided Benign:3
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | TCN2: BP4 - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Aug 15, 2017 | BS1, BS2, BP1, BP4; This alteration has an allele frequency that is greater than expected for the associated disease, was seen in a healthy adult where full penetrance of the disorder is expected at an early age, is a missense alteration in a gene for which primarily truncating variants are known to cause disease, and is predicted to be tolerated by multiple functional prediction tools. - |
TCN2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 01, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at