chr18-31386689-TG-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_177986.5(DSG4):c.87del(p.Lys30ArgfsTer54) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
DSG4
NM_177986.5 frameshift, splice_region
NM_177986.5 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0980
Genes affected
DSG4 (HGNC:21307): (desmoglein 4) This gene encodes a member of the desmoglein subgroup of desmosomal cadherins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a transmembrane component of desmosomes and may play a role in cell-cell adhesion in epithelial cells. Mutations in the gene are associated with localized autosomal recessive hypotrichosis and monilethrix, characterized by impaired hair growth. [provided by RefSeq, May 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 18-31386689-TG-T is Pathogenic according to our data. Variant chr18-31386689-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 2720.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSG4 | NM_177986.5 | c.87del | p.Lys30ArgfsTer54 | frameshift_variant, splice_region_variant | 3/16 | ENST00000308128.9 | |
DSG1-AS1 | NR_110788.1 | n.157-32237del | intron_variant, non_coding_transcript_variant | ||||
DSG4 | NM_001134453.3 | c.87del | p.Lys30ArgfsTer54 | frameshift_variant, splice_region_variant | 3/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSG4 | ENST00000308128.9 | c.87del | p.Lys30ArgfsTer54 | frameshift_variant, splice_region_variant | 3/16 | 1 | NM_177986.5 | P2 | |
DSG1-AS1 | ENST00000581856.5 | n.96-32237del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
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?
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250802Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135504
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460770Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 726672
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hypotrichosis 6 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2007 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at