2-105361318-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001318895.3(FHL2):c.805G>A(p.Asp269Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001318895.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251018Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135704
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461736Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727176
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with FHL2-related conditions. This variant is present in population databases (rs770706113, gnomAD 0.01%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 269 of the FHL2 protein (p.Asp269Asn). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at