NM_022802.3:c.2562G>C

Variant names:

• chr10-124993299-C-G
• rs74769610
• NM_001329.4:c.942G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_022802.3(CTBP2):​c.2562G>C​(p.Pro854Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CTBP2 NM_022802.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.231
• Publications: 5 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 10-124993299-C-G is Benign according to our data. Variant chr10-124993299-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2681218.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.231 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022802.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	NM_001329.4	MANE Select	c.942G>C	p.Pro314Pro	synonymous	Exon 9 of 11	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.2562G>C	p.Pro854Pro	synonymous	Exon 7 of 9	NP_073713.2	P56545-2
	CTBP2	NM_001363508.2		c.1146G>C	p.Pro382Pro	synonymous	Exon 7 of 9	NP_001350437.1	P56545-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.942G>C	p.Pro314Pro	synonymous	Exon 9 of 11	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.2562G>C	p.Pro854Pro	synonymous	Exon 7 of 9	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000334808.10	TSL:1	c.1146G>C	p.Pro382Pro	synonymous	Exon 7 of 9	ENSP00000357816.5	P56545-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		-0.23
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs74769610; hg19: chr10-126681868;