chr2-215435742-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_212482.4(FN1):c.61G>A(p.Val21Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000125 in 1,605,000 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 (★★). Synonymous variant affecting the same amino acid position (i.e. V21V) has been classified as Likely benign.
Frequency
Consequence
NM_212482.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1452844Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 721858
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Spondylometaphyseal dysplasia - Sutcliffe type;C1866075:Glomerulopathy with fibronectin deposits 2 Uncertain:1
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not provided Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 21 of the FN1 protein (p.Val21Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FN1-related conditions. 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 FN1 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