1-152304999-G-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_002016.2(FLG):c.9887C>A(p.Ser3296*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_002016.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151974Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251480Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135912
GnomAD4 exome AF: 0.0000540 AC: 79AN: 1461846Hom.: 0 Cov.: 37 AF XY: 0.0000454 AC XY: 33AN XY: 727218
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151974Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74210
ClinVar
Submissions by phenotype
Ichthyosis vulgaris Pathogenic:3
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This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported in multiple patients with ichthyosis vulgaris or atopic dermatitis [PMID 18200065, 28120571, 25997159, 27519469] -
not provided Pathogenic:1
Observed in the heterozygous state as well as with a second loss-of-function FLG variant in individuals with ichthyosis vulgaris with or without atopic dermatitis in the published literature (PMID: 27519469, 18200065); Nonsense variant predicted to result in protein truncation, as the last 766 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 27519469, 18200065, 28120571, 35870561, 25997159) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at