rs144442113
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001318895.3(FHL2):āc.521T>Cā(p.Val174Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,609,438 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V174D) 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.521T>C | p.Val174Ala | missense_variant | 6/7 | ENST00000530340.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FHL2 | ENST00000530340.6 | c.521T>C | p.Val174Ala | missense_variant | 6/7 | 1 | NM_001318895.3 | P1 | |
ENST00000457290.2 | n.40+375A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000791 AC: 12AN: 151730Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000166 AC: 4AN: 240304Hom.: 0 AF XY: 0.00000770 AC XY: 1AN XY: 129818
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1457708Hom.: 0 Cov.: 32 AF XY: 0.00000690 AC XY: 5AN XY: 724702
GnomAD4 genome ? AF: 0.0000791 AC: 12AN: 151730Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4AN XY: 74092
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 174 of the FHL2 protein (p.Val174Ala). This variant is present in population databases (rs144442113, gnomAD 0.02%). 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: 580914). 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