rs863223631
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001110556.2(FLNA):c.2254_2268delinsCCCTTCAGGGTG(p.Val752_Asn756delinsProPheArgVal) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Consequence
FLNA
NM_001110556.2 protein_altering
NM_001110556.2 protein_altering
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.94
Genes affected
FLNA (HGNC:3754): (filamin A) The protein encoded by this gene is an actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins. The encoded protein is involved in remodeling the cytoskeleton to effect changes in cell shape and migration. This protein interacts with integrins, transmembrane receptor complexes, and second messengers. Defects in this gene are a cause of several syndromes, including periventricular nodular heterotopias (PVNH1, PVNH4), otopalatodigital syndromes (OPD1, OPD2), frontometaphyseal dysplasia (FMD), Melnick-Needles syndrome (MNS), and X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.2254_2268delinsCCCTTCAGGGTG | p.Val752_Asn756delinsProPheArgVal | protein_altering_variant | 15/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.2254_2268delinsCCCTTCAGGGTG | p.Val752_Asn756delinsProPheArgVal | protein_altering_variant | 15/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.2254_2268delinsCCCTTCAGGGTG | p.Val752_Asn756delinsProPheArgVal | protein_altering_variant | 15/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2017 | This variant, c.2254_2268delinsCCCTTCAGGGTG, is a complex sequence change that results in the deletion of five amino acids of the FLNA protein and the insertion of four amino acids (p.Val752_Asn756delinsProPheArgVal). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FLNA-related disease. In summary, this variant is a novel in-frame complex sequence change and the impact of this change is uncertain. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at