Variant 10-125026145-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_022802.3(CTBP2):c.1615C>G(p.Gln539Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,605,108 control chromosomes in the GnomAD database, including 189,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 16663 hom., cov: 33)

Exomes 𝑓: 0.49 ( 172984 hom. )

Consequence

CTBP2
NM_022802.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.86

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8411875E-4).

BP6

Variant 10-125026145-G-C is Benign according to our data. Variant chr10-125026145-G-C is described in ClinVar as [Benign]. Clinvar id is 3059384.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTBP2	NM_022802.3 linkuse as main transcript	c.1615C>G	p.Gln539Glu	missense_variant	1/9	ENST00000309035.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTBP2	ENST00000309035.11 linkuse as main transcript	c.1615C>G	p.Gln539Glu	missense_variant	1/9	1	NM_022802.3		P56545-2

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70181

AN:

152010

Hom.:

16652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.475

AC:

117146

AN:

246448

Hom.:

28839

AF XY:

0.480

AC XY:

63909

AN XY:

133166

show subpopulations

Gnomad AFR exome

AF:

0.375

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.476

Gnomad EAS exome

AF:

0.648

Gnomad SAS exome

AF:

0.452

Gnomad FIN exome

AF:

0.562

Gnomad NFE exome

AF:

0.495

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.485

AC:

704806

AN:

1452980

Hom.:

172984

Cov.:

AF XY:

0.485

AC XY:

349765

AN XY:

721088

show subpopulations

Gnomad4 AFR exome

AF:

0.385

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.473

Gnomad4 EAS exome

AF:

0.585

Gnomad4 SAS exome

AF:

0.448

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.490

Gnomad4 OTH exome

AF:

0.484

GnomAD4 genome

AF:

0.462

AC:

70229

AN:

152128

Hom.:

16663

Cov.:

AF XY:

0.465

AC XY:

34548

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.386

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.476

Gnomad4 EAS

AF:

0.628

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.580

Gnomad4 NFE

AF:

0.496

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.474

Hom.:

12825

Bravo

AF:

0.441

TwinsUK

AF:

0.486

AC:

1801

ALSPAC

AF:

0.479

AC:

1847

ESP6500AA

AF:

0.385

AC:

1695

ESP6500EA

AF:

0.496

AC:

4263

ExAC

AF:

0.479

AC:

58112

Asia WGS

AF:

0.560

AC:

1952

AN:

3478

EpiCase

AF:

0.490

EpiControl

AF:

0.482

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CTBP2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

-0.40

BayesDel_noAF

Benign

-0.20

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.56

MetaRNN

Benign

0.00018

MetaSVM

Benign

-0.90

MutationTaster

Benign

0.012

P;P;P;P;P

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.37

REVEL

Uncertain

0.35

Sift

Benign

0.086

Sift4G

Benign

0.23

Polyphen

0.93

Vest4

0.12

MPC

0.12

ClinPred

0.040

GERP RS

5.3

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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