Genetic Variant CTBP2:p.Gly117Ser (chr10-125002969-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP5BS2

The NM_001329.4(CTBP2):c.349G>A(p.Gly117Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,612,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CTBP2
NM_001329.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.16

Publications

7 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP5

Variant 10-125002969-C-T is Pathogenic according to our data. Variant chr10-125002969-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 1696855.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTBP2	NM_001329.4	MANE Select	c.349G>A	p.Gly117Ser	missense	Exon 5 of 11	NP_001320.1	P56545-1
CTBP2	NM_022802.3		c.1969G>A	p.Gly657Ser	missense	Exon 3 of 9	NP_073713.2	P56545-2
CTBP2	NM_001363508.2		c.553G>A	p.Gly185Ser	missense	Exon 3 of 9	NP_001350437.1	P56545-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.349G>A	p.Gly117Ser	missense	Exon 5 of 11	ENSP00000338615.5	P56545-1
CTBP2	ENST00000309035.11	TSL:1	c.1969G>A	p.Gly657Ser	missense	Exon 3 of 9	ENSP00000311825.6	P56545-2
CTBP2	ENST00000334808.10	TSL:1	c.553G>A	p.Gly185Ser	missense	Exon 3 of 9	ENSP00000357816.5	P56545-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250488

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460470

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726558

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52924

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5170

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111874

Other (OTH)

AF:

0.00

AC:

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Pulmonary artery atresia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

Eigen

Benign

0.017

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.85

M_CAP

Benign

0.080

MetaRNN

Uncertain

0.65

MetaSVM

Uncertain

-0.021

MutationAssessor

Benign

-1.0

PhyloP100

6.2

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.57

Sift

Benign

0.069

Sift4G

Benign

0.42

Polyphen

0.96

Vest4

0.71

MutPred

0.34

Loss of catalytic residue at A184 (P = 0.0537)

MVP

0.83

MPC

1.1

ClinPred

0.85

GERP RS

3.8

Varity_R

0.83

gMVP

0.82

Mutation Taster

=24/76

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over