Variant 10-125005601-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The ENST00000334808.10(CTBP2):c.208G>A(p.Gly70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 1,612,740 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.014 ( 25 hom., cov: 32)

Exomes 𝑓: 0.020 ( 367 hom. )

Consequence

CTBP2
ENST00000334808.10 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.57

Variant links:

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]

CTBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 10-125005601-C-T is Benign according to our data. Variant chr10-125005601-C-T is described in ClinVar as [Benign]. Clinvar id is 3042376.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0137 (2090/152358) while in subpopulation NFE AF= 0.0221 (1502/68024). AF 95% confidence interval is 0.0212. There are 25 homozygotes in gnomad4. There are 1015 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2090 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTBP2	NM_022802.3 linkuse as main transcript	c.1679-2109G>A		intron_variant		ENST00000309035.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTBP2	ENST00000309035.11 linkuse as main transcript	c.1679-2109G>A		intron_variant		1	NM_022802.3		P56545-2

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2091

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00326

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00942

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00809

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0221

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0157

AC:

3792

AN:

241022

Hom.:

AF XY:

0.0166

AC XY:

2195

AN XY:

132372

show subpopulations

Gnomad AFR exome

AF:

0.00337

Gnomad AMR exome

AF:

0.00716

Gnomad ASJ exome

AF:

0.0259

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.0157

Gnomad FIN exome

AF:

0.00850

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0203

AC:

29624

AN:

1460382

Hom.:

367

Cov.:

AF XY:

0.0203

AC XY:

14743

AN XY:

726460

show subpopulations

Gnomad4 AFR exome

AF:

0.00305

Gnomad4 AMR exome

AF:

0.00808

Gnomad4 ASJ exome

AF:

0.0256

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0158

Gnomad4 FIN exome

AF:

0.00984

Gnomad4 NFE exome

AF:

0.0229

Gnomad4 OTH exome

AF:

0.0178

GnomAD4 genome

AF:

0.0137

AC:

2090

AN:

152358

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1015

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00325

Gnomad4 AMR

AF:

0.00934

Gnomad4 ASJ

AF:

0.0320

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.00809

Gnomad4 NFE

AF:

0.0221

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0189

Hom.:

Bravo

AF:

0.0133

ESP6500AA

AF:

0.00285

AC:

ESP6500EA

AF:

0.0224

AC:

ExAC

AF:

0.0159

AC:

1877

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0236

EpiControl

AF:

0.0209

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

Feb 20, 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

4.9

DANN

Benign

0.84

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.77

MutationTaster

Benign

1.0

N;N;N;N;N;N

PROVEAN

Benign

-0.62

REVEL

Benign

0.19

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Vest4

0.030

MutPred

0.54

Gain of solvent accessibility (P = 6e-04);

ClinPred

0.0062

GERP RS

-1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: -1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over