19-855649-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_001972.4(ELANE):c.452G>T(p.Cys151Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C151S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001972.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1454638Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 723938
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
To our knowledge, this substitution has neither been published as a mutation, nor reported as a benign polymorphism. However, another missense substitution at this same position, C151S aka C122S, has been reported in association with Severe Congenital Neutropenia (Ancliff et al., 2001; Karlsson et al., 2007). Therefore, we consider C151F a mutation and its presence consistent with a diagnosis of ELANE-related neutropenia. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at