rs1557177229
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP3
The NM_001110556.2(FLNA):c.4721_4732del(p.Asp1574_Glu1577del) variant causes a inframe deletion 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 (★). Synonymous variant affecting the same amino acid position (i.e. D1574D) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 24)
Consequence
FLNA
NM_001110556.2 inframe_deletion
NM_001110556.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.91
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 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_001110556.2.
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.4721_4732del | p.Asp1574_Glu1577del | inframe_deletion | 28/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.4721_4732del | p.Asp1574_Glu1577del | inframe_deletion | 28/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.4721_4732del | p.Asp1574_Glu1577del | inframe_deletion | 28/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
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 | Jul 07, 2017 | 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. A missense substitution within the deleted amino acids (p.Gly1576Arg) has been determined to be pathogenic (PMID: 26686323, 26804200). This suggests that the glycine residue is critical for FLNA protein function. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. This variant has not been reported in the literature in individuals with FLNA-related disease. This variant is not present in population databases (ExAC no frequency). This variant, c.4721_4732del, results in the deletion of 4 amino acids of the FLNA protein (p.Asp1574_Glu1577del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at