15-42777086-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_173500.4(TTBK2):c.1354G>A(p.Glu452Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,614,110 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E452E) has been classified as Likely benign.
Frequency
Consequence
NM_173500.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTBK2 | NM_173500.4 | c.1354G>A | p.Glu452Lys | missense_variant | 12/15 | ENST00000267890.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTBK2 | ENST00000267890.11 | c.1354G>A | p.Glu452Lys | missense_variant | 12/15 | 5 | NM_173500.4 | P1 | |
TTBK2 | ENST00000567840.5 | c.1354G>A | p.Glu452Lys | missense_variant | 12/12 | 1 | |||
TTBK2 | ENST00000567274.5 | c.1249G>A | p.Glu417Lys | missense_variant | 11/11 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000373 AC: 93AN: 249280Hom.: 1 AF XY: 0.000518 AC XY: 70AN XY: 135232
GnomAD4 exome AF: 0.000217 AC: 317AN: 1461866Hom.: 5 Cov.: 31 AF XY: 0.000304 AC XY: 221AN XY: 727238
GnomAD4 genome AF: 0.000138 AC: 21AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74438
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2023 | The c.1354G>A (p.E452K) alteration is located in exon 12 (coding exon 11) of the TTBK2 gene. This alteration results from a G to A substitution at nucleotide position 1354, causing the glutamic acid (E) at amino acid position 452 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 30, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
TTBK2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 13, 2019 | This variant is classified as likely 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