rs1557178202
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4BP6_Moderate
The NM_001110556.2(FLNA):āc.2584A>Gā(p.Ile862Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,209,113 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 Likely benign (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I862T) has been classified as Likely benign.
Frequency
Consequence
NM_001110556.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.2584A>G | p.Ile862Val | missense_variant | 18/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.2584A>G | p.Ile862Val | missense_variant | 18/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.2584A>G | p.Ile862Val | missense_variant | 18/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000895 AC: 1AN: 111708Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33912
GnomAD3 exomes AF: 0.00000553 AC: 1AN: 180951Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67303
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097405Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 363073
GnomAD4 genome ? AF: 0.00000895 AC: 1AN: 111708Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33912
ClinVar
Submissions by phenotype
Heterotopia, periventricular, X-linked dominant Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genomics Laboratory, Stanford Medicine | Jun 22, 2021 | The p.Ile862Val variant in the FLNA gene has not been previously reported in association with disease. The p.Ile862Val variant has been identified in 1/27,369 Latino chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). While this variant was present in one individual in gnomAD, this individual is female, and this variant was not observed in any males. Given the possibility of milder phenotypes as discussed above, criteria for low frequency in the general population was applied. The FLNA gene has fewer missense variants in the general population than expected. A low rate of missense variation may suggest that this gene is intolerant to missense variation. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Ile862Val variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2; PP2] - |
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 | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at