10-125005537-G-A

Variant names:

• chr10-125005537-G-A
• rs201342709
• NM_022802.3:c.1679-2045C>T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_022802.3(CTBP2):​c.1679-2045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000931 in 1,605,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (0 hom.)
• Consequence: CTBP2 NM_022802.3 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.13

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

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-125005537-G-A is Benign according to our data. Variant chr10-125005537-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3037773.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBP2	NM_022802.3	c.1679-2045C>T		intron_variant	Intron 1 of 8	ENST00000309035.11	NP_073713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTBP2	ENST00000309035.11	c.1679-2045C>T		intron_variant	Intron 1 of 8	1	NM_022802.3	ENSP00000311825.6
CTBP2	ENST00000337195.10	c.59-2045C>T		intron_variant	Intron 3 of 10	1		ENSP00000338615.5

Frequencies

GnomAD3 genomes AF: 0.000729 AC: 111 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000747 AC: 172 AN: 230398 Hom.: 0 AF XY: 0.000742 AC XY: 94 AN XY: 126628

Gnomad AFR exome AF: 0.0000759

Gnomad AMR exome AF: 0.0000301

Gnomad ASJ exome AF: 0.000105

Gnomad EAS exome AF: 0.000117

Gnomad SAS exome AF: 0.0000340

Gnomad FIN exome AF: 0.000670

Gnomad NFE exome AF: 0.00146

Gnomad OTH exome AF: 0.000692

GnomAD4 exome AF: 0.000952 AC: 1383 AN: 1452846 Hom.: 0 Cov.: 31 AF XY: 0.000940 AC XY: 679 AN XY: 722034

Gnomad4 AFR exome AF: 0.0000601

Gnomad4 AMR exome AF: 0.0000457

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.0000762

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00106

Gnomad4 NFE exome AF: 0.00115

Gnomad4 OTH exome AF: 0.000732

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000631 AC XY: 47 AN XY: 74466

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000943

Gnomad4 NFE AF: 0.00131

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000940 Hom.: 0

Bravo AF: 0.000620

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CTBP2-related disorder Benign:1

Apr 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs201342709; hg19: chr10-126694106;