2-105386455-A-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001318895.3(FHL2):c.62T>A(p.Leu21Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000396 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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 Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152254Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251486Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135918
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727244
GnomAD4 genome AF: 0.000204 AC: 31AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74386
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Leu21Gln variant in FHL2 not been previously reported in individuals with cardiomyopathy, but has been identified in 2/66712 European chromosomes by the E xome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs75580 5016). Computational prediction tools and conservation analysis do not provide s trong support for or against an impact to the protein. In summary, the clinical significance of the p.Leu21Gln variant is uncertain. -
Primary dilated cardiomyopathy Uncertain:1
This variant has not been reported in the literature in individuals affected with FHL2-related conditions. This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 21 of the FHL2 protein (p.Leu21Gln). This variant is present in population databases (rs755805016, gnomAD 0.006%). ClinVar contains an entry for this variant (Variation ID: 504936). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at