2-105361303-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001318895.3(FHL2):c.820G>A(p.Asp274Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,538 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 Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250462Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135336
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461236Hom.: 0 Cov.: 29 AF XY: 0.00000550 AC XY: 4AN XY: 726884
GnomAD4 genome AF: 0.0000919 AC: 14AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74476
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 274 of the FHL2 protein (p.Asp274Asn). This variant is present in population databases (rs145070796, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with FHL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 948240). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FHL2 protein function with a negative predictive value of 80%. 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