rs782450368
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001110556.2(FLNA):c.1580G>A(p.Arg527His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,097,753 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R527C) has been classified as Likely benign.
Frequency
Consequence
NM_001110556.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.1580G>A | p.Arg527His | missense_variant | 11/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.1580G>A | p.Arg527His | missense_variant | 11/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.1580G>A | p.Arg527His | missense_variant | 11/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 112835Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34975 FAILED QC
GnomAD3 exomes AF: 0.0000165 AC: 3AN: 181546Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67624
GnomAD4 exome AF: 0.0000273 AC: 30AN: 1097753Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 11AN XY: 363345
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 112835Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34975
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 18, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 13, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 22, 2016 | - - |
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at