chr11-57804691-CGC-TAG

Variant names:

• chr11-57804691-CGC-TAG
• NM_001085458.2:c.1633_1635delCGCinsTAG
• CTNND1 p.Arg545*

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_001085458.2(CTNND1):​c.1633_1635delCGCinsTAG​(p.Arg545*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNND1 NM_001085458.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• 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: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND1	NM_001085458.2	MANE Select	c.1633_1635delCGCinsTAG	p.Arg545*	stop_gained	N/A	NP_001078927.1	O60716-1
	CTNND1	NM_001085459.2		c.1633_1635delCGCinsTAG	p.Arg545*	stop_gained	N/A	NP_001078928.1	O60716-2
	CTNND1	NM_001331.3		c.1633_1635delCGCinsTAG	p.Arg545*	stop_gained	N/A	NP_001322.1	O60716-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND1	ENST00000399050.10	TSL:1 MANE Select	c.1633_1635delCGCinsTAG	p.Arg545*	stop_gained	N/A	ENSP00000382004.5	O60716-1
	CTNND1	ENST00000361332.8	TSL:1	c.1633_1635delCGCinsTAG	p.Arg545*	stop_gained	N/A	ENSP00000354823.4	O60716-2
	CTNND1	ENST00000361391.10	TSL:1	c.1633_1635delCGCinsTAG	p.Arg545*	stop_gained	N/A	ENSP00000354785.6	O60716-6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-57572163;