rs371563857
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_001110556.2(FLNA):c.7157A>G(p.Asp2386Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,209,765 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001110556.2 missense, splice_region
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.7157A>G | p.Asp2386Gly | missense_variant, splice_region_variant | 45/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.7133A>G | p.Asp2378Gly | missense_variant, splice_region_variant | 44/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.7157A>G | p.Asp2386Gly | missense_variant, splice_region_variant | 45/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000177 AC: 2AN: 112704Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 34874
GnomAD3 exomes AF: 0.0000165 AC: 3AN: 181404Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67334
GnomAD4 exome AF: 0.00000638 AC: 7AN: 1097061Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 2AN XY: 362579
GnomAD4 genome ? AF: 0.0000177 AC: 2AN: 112704Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 34874
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 | Oct 13, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 570374). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is present in population databases (rs371563857, gnomAD 0.006%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2378 of the FLNA protein (p.Asp2378Gly). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at