18-31392200-C-T
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_177986.5(DSG4):c.865C>T(p.Arg289*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
DSG4
NM_177986.5 stop_gained
NM_177986.5 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 0.635
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 Pathogenic. Variant got 11 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 18-31392200-C-T is Pathogenic according to our data. Variant chr18-31392200-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2726.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152050Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251076Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135696
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461474Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727040
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152050Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74260
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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 | Jun 01, 2006 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
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Benign
FATHMM_MKL
Uncertain
D
Vest4
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at