rs968230475
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP2PP3BP6BS2
The ENST00000369850.10(FLNA):āc.6268G>Cā(p.Val2090Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000735 in 1,210,682 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2090A) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000369850.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.6268G>C | p.Val2090Leu | missense_variant | 39/48 | ENST00000369850.10 | NP_001104026.1 | |
FLNA | NM_001456.4 | c.6244G>C | p.Val2082Leu | missense_variant | 38/47 | NP_001447.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.6268G>C | p.Val2090Leu | missense_variant | 39/48 | 1 | NM_001110556.2 | ENSP00000358866 |
Frequencies
GnomAD3 genomes AF: 0.0000177 AC: 2AN: 112789Hom.: 0 Cov.: 25 AF XY: 0.0000286 AC XY: 1AN XY: 34931
GnomAD3 exomes AF: 0.0000165 AC: 3AN: 181661Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67627
GnomAD4 exome AF: 0.0000792 AC: 87AN: 1097893Hom.: 0 Cov.: 32 AF XY: 0.0000660 AC XY: 24AN XY: 363381
GnomAD4 genome AF: 0.0000177 AC: 2AN: 112789Hom.: 0 Cov.: 25 AF XY: 0.0000286 AC XY: 1AN XY: 34931
ClinVar
Submissions by phenotype
Wolff-Parkinson-White pattern Uncertain:1
Uncertain significance, no assertion criteria provided | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Jul 14, 2017 | This variant was identified in an individual with Wolff-Parkinson-White syndrome - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2023 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function - |
Heterotopia, periventricular, X-linked dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | May 21, 2020 | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as VOUS. Following criteria are met: 0103 - Both loss- and gain-of-function are known mechanisms of disease for this gene (Cannaerts, E. et al. (2018)). (N) 0109 - This gene is known to be associated with X-linked recessive disease. (N) 0110 - This gene is known to be associated with X-linked dominant disease. (N) 0112 - Variants in this gene are known to have reduced penetrance (Cannaerts, E. et al. (2018)). (N) 0200 - Variant is predicted to result in a missense amino acid change from valine to leucine (exon 39). (N) 0253 - Variant is hemizygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (3 heterozygotes, 0 homozygote, 0 hemizygote). (P) 0502 - Missense variant with conflicting in-silico predictions and/or uninformative conservation (MutationAssessor, FATHMM, PolyPhen2, PROVEAN, UCSC). (N) 0600 - Variant is located in an annotated domain or motif (Filamin/ABP280 repeat domain; PDB) (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0804 - Variant has previously been described as variant of uncertain significance (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign - |
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 02, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at