chr11-57796640-CT-C

Variant names:

• chr11-57796640-CT-C
• rs1555053981
• NM_001085458.2:c.606delT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001085458.2(CTNND1):​c.606delT​(p.Pro203LeufsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CTNND1 NM_001085458.2 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

Genes affected

CTNND1 (HGNC:2515): (catenin delta 1) This gene encodes a member of the Armadillo protein family, which function in adhesion between cells and signal transduction. Multiple translation initiation codons and alternative splicing result in many different isoforms being translated. Not all of the full-length natures of the described transcript variants have been determined. Read-through transcription also exists between this gene and the neighboring upstream thioredoxin-related transmembrane protein 2 (TMX2) gene. [provided by RefSeq, Dec 2010]

ENSG00000288534 (HGNC:):

TMX2-CTNND1 (HGNC:41992): (TMX2-CTNND1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring TMX2 (thioredoxin-related transmembrane protein 2) and CTNND1 (catenin, cadherin-associated protein, delta 1) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-57796640-CT-C is Pathogenic according to our data. Variant chr11-57796640-CT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 438817.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085458.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND1	NM_001085458.2	MANE Select	c.606delT	p.Pro203LeufsTer32	frameshift	Exon 6 of 21	NP_001078927.1
	CTNND1	NM_001085459.2		c.606delT	p.Pro203LeufsTer32	frameshift	Exon 6 of 20	NP_001078928.1
	CTNND1	NM_001331.3		c.606delT	p.Pro203LeufsTer32	frameshift	Exon 6 of 19	NP_001322.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND1	ENST00000399050.10	TSL:1 MANE Select	c.606delT	p.Pro203LeufsTer32	frameshift	Exon 6 of 21	ENSP00000382004.5
	CTNND1	ENST00000361332.8	TSL:1	c.606delT	p.Pro203LeufsTer32	frameshift	Exon 6 of 20	ENSP00000354823.4
	CTNND1	ENST00000361391.10	TSL:1	c.606delT	p.Pro203LeufsTer32	frameshift	Exon 6 of 19	ENSP00000354785.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Blepharocheilodontic syndrome 2 Pathogenic:2

Sep 20, 2017

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Jul 04, 2023

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs1555053981; hg19: chr11-57564112;