ENST00000309035.11:c.700G>C

Variant names:

• chr10-125027060-C-G
• rs3781409
• ENST00000309035.11:c.700G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000309035.11(CTBP2):​c.700G>C​(p.Val234Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V234M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CTBP2 ENST00000309035.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBP2	NM_001329.4	c.58+11937G>C		intron_variant	Intron 3 of 10	ENST00000337195.11	NP_001320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTBP2	ENST00000337195.11	c.58+11937G>C		intron_variant	Intron 3 of 10	1	NM_001329.4	ENSP00000338615.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 94

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.11
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.040	T
PhyloP100		3.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.23
Sift	Benign	0.076	T
Sift4G	Benign	0.14	T
Polyphen		0.047	B
Vest4		0.53
MutPred		0.12		Gain of glycosylation at P236 (P = 0.1261);
MVP		0.79
MPC		0.50
ClinPred		0.98	D
GERP RS		3.6
gMVP		0.18
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs3781409; hg19: chr10-126715629;