rs3781409
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_022802.3(CTBP2):c.700G>A(p.Val234Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,613,106 control chromosomes in the GnomAD database, including 53,878 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.22 ( 3951 hom., cov: 33)
Exomes 𝑓: 0.26 ( 49927 hom. )
Consequence
CTBP2
NM_022802.3 missense
NM_022802.3 missense
Scores
1
4
10
Clinical Significance
Conservation
PhyloP100: 3.06
Genes affected
CTBP2 (HGNC:2495): (C-terminal binding protein 2) This gene produces alternative transcripts encoding two distinct proteins. One protein is a transcriptional repressor, while the other isoform is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3' untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.001383245).
BP6
Variant 10-125027060-C-T is Benign according to our data. Variant chr10-125027060-C-T is described in ClinVar as [Benign]. Clinvar id is 3059060.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTBP2 | NM_022802.3 | c.700G>A | p.Val234Met | missense_variant | 1/9 | ENST00000309035.11 | NP_073713.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTBP2 | ENST00000309035.11 | c.700G>A | p.Val234Met | missense_variant | 1/9 | 1 | NM_022802.3 | ENSP00000311825.6 | ||
CTBP2 | ENST00000337195.10 | c.58+11937G>A | intron_variant | 1 | ENSP00000338615.5 |
Frequencies
GnomAD3 genomes AF: 0.216 AC: 32917AN: 152114Hom.: 3951 Cov.: 33
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GnomAD3 exomes AF: 0.240 AC: 59750AN: 249338Hom.: 7478 AF XY: 0.238 AC XY: 32126AN XY: 135242
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GnomAD4 exome AF: 0.259 AC: 378277AN: 1460874Hom.: 49927 Cov.: 94 AF XY: 0.257 AC XY: 186631AN XY: 726638
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GnomAD4 genome AF: 0.216 AC: 32924AN: 152232Hom.: 3951 Cov.: 33 AF XY: 0.214 AC XY: 15917AN XY: 74446
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1034
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
CTBP2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 28, 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
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Pathogenic
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MPC
ClinPred
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at