rs782090266
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PP2PP3_ModerateBP6
The NM_001110556.2(FLNA):c.1138G>A(p.Asp380Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,097,958 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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). Synonymous variant affecting the same amino acid position (i.e. D380D) has been classified as Likely benign.
Frequency
Consequence
NM_001110556.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.1138G>A | p.Asp380Asn | missense_variant | 8/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.1138G>A | p.Asp380Asn | missense_variant | 8/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.1138G>A | p.Asp380Asn | missense_variant | 8/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? Cov.: 25
GnomAD3 exomes AF: 0.00000551 AC: 1AN: 181452Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67536
GnomAD4 exome AF: 0.0000155 AC: 17AN: 1097958Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 3AN XY: 363362
GnomAD4 genome ? Cov.: 25
ClinVar
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 | Dec 24, 2021 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLNA protein function. ClinVar contains an entry for this variant (Variation ID: 561301). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is present in population databases (rs782090266, gnomAD 0.001%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 380 of the FLNA protein (p.Asp380Asn). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID 561301; Landrum et al., 2016) - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Jun 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at