2-105361398-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001318895.3(FHL2):c.725G>A(p.Arg242Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R242W) has been classified 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FHL2 | NM_001318895.3 | c.725G>A | p.Arg242Gln | missense_variant | 7/7 | ENST00000530340.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FHL2 | ENST00000530340.6 | c.725G>A | p.Arg242Gln | missense_variant | 7/7 | 1 | NM_001318895.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249520Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135040
GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461762Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727182
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74460
ClinVar
Submissions by phenotype
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 12, 2018 | - - |
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2021 | This variant is present in population databases (rs188279857, ExAC 0.004%). This sequence change replaces arginine with glutamine at codon 242 of the FHL2 protein (p.Arg242Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant has not been reported in the literature in individuals with FHL2-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at