NM_001988.4:c.6082_6084delGTCinsTTT

Variant names:

• chr17-76007121-GAC-AAA
• NM_001988.4:c.6082_6084delGTCinsTTT
• EVPL p.Val2028Phe

Variant summary

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

The NM_001988.4(EVPL):​c.6082_6084delGTCinsTTT​(p.Val2028Phe) variant causes a missense change involving the alteration of a non-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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2028I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EVPL NM_001988.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 0 publications found

Genes affected

EVPL (HGNC:3503): (envoplakin) This gene encodes a member of the plakin family of proteins that forms a component of desmosomes and the epidermal cornified envelope. This gene is located in the tylosis oesophageal cancer locus on chromosome 17q25, and its deletion is associated with both familial and sporadic forms of oesophageal squamous cell carcinoma. Patients suffering from the autoimmune mucocutaneous disorder, paraneoplastic pemphigus, develop antibodies against the encoded protein. [provided by RefSeq, Jul 2016]

EVPL Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001988.4. 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
	EVPL	NM_001988.4	MANE Select	c.6082_6084delGTCinsTTT	p.Val2028Phe	missense	N/A	NP_001979.2	Q92817
	EVPL	NM_001320747.2		c.6148_6150delGTCinsTTT	p.Val2050Phe	missense	N/A	NP_001307676.1	K7EKI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVPL	ENST00000301607.8	TSL:1 MANE Select	c.6082_6084delGTCinsTTT	p.Val2028Phe	missense	N/A	ENSP00000301607.3	Q92817
	EVPL	ENST00000586740.1	TSL:1	c.6148_6150delGTCinsTTT	p.Val2050Phe	missense	N/A	ENSP00000465630.1	K7EKI0
	EVPL	ENST00000870829.1		c.6022_6024delGTCinsTTT	p.Val2008Phe	missense	N/A	ENSP00000540888.1

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		-0.11

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: chr17-74003202;