rs267606817
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP2PP3_StrongPP5
The NM_001110556.2(FLNA):c.2132T>A(p.Val711Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 22)
Consequence
FLNA
NM_001110556.2 missense
NM_001110556.2 missense
Scores
9
6
2
Clinical Significance
Conservation
PhyloP100: 4.21
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 Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, FLNA
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.964
PP5
?
Variant X-154364263-A-T is Pathogenic according to our data. Variant chrX-154364263-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 11778.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-154364263-A-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.2132T>A | p.Val711Asp | missense_variant | 14/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.2132T>A | p.Val711Asp | missense_variant | 14/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.2132T>A | p.Val711Asp | missense_variant | 14/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cardiac valvular dysplasia, X-linked Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 02, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D;.;.;.;.
FATHMM_MKL
Benign
D
LIST_S2
Pathogenic
D;D;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;.;D;D;.
Sift4G
Uncertain
D;D;D;D;D
Polyphen
P;.;B;B;.
Vest4
MutPred
Gain of disorder (P = 0.0132);.;Gain of disorder (P = 0.0132);Gain of disorder (P = 0.0132);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at