X-154364033-TGTTGGGGATGCTGAC-TCCCTTCAGGGTG
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001110556.2(FLNA):c.2254_2268delinsCACCCTGAAGGG(p.Val752_Asn756delinsHisProGluGly) 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]
Genome browser will be placed here
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_2268delinsCACCCTGAAGGG | p.Val752_Asn756delinsHisProGluGly | protein_altering_variant | 15/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.2254_2268delinsCACCCTGAAGGG | p.Val752_Asn756delinsHisProGluGly | protein_altering_variant | 15/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.2254_2268delinsCACCCTGAAGGG | p.Val752_Asn756delinsHisProGluGly | 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
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2014 | The c.2254_2268del15ins12 variant has not been published as a disease-causing mutation or as a benign polymorphism, to our knowledge. The c.2254_2268del15ins12 variant results in a deletion of five amino acids and an insertion of four amino acids (V752_N756delinsPFRV). This deletion/insertion event crosses the splice junction; splice prediction algorithms predict that this change may result in creation of a crytpic splice donor site upstream of the natural donor site. This cryptic site, if it occurs in vivo, is predicted to result in the same deletion of five amino acids but an insertion of three amino acids (V752_N756delinsPFR). Mutations in the FLNA gene have been reported to co-segregate in four unrelated families with X-linked recessive nonsyndromic cardiac valvular dystrophy (Kyndt et al., 2007).Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD,FLNA - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at