rs371724771
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_001110556.2(FLNA):c.7649C>T(p.Pro2550Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,210,820 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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. P2550P) has been classified as Likely benign.
Frequency
Consequence
NM_001110556.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.7649C>T | p.Pro2550Leu | missense_variant | 47/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.7625C>T | p.Pro2542Leu | missense_variant | 46/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.7649C>T | p.Pro2550Leu | missense_variant | 47/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes AF: 0.0000264 AC: 3AN: 113792Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 35906
GnomAD3 exomes AF: 0.0000331 AC: 6AN: 181242Hom.: 0 AF XY: 0.0000741 AC XY: 5AN XY: 67458
GnomAD4 exome AF: 0.0000319 AC: 35AN: 1097028Hom.: 0 Cov.: 33 AF XY: 0.0000496 AC XY: 18AN XY: 362656
GnomAD4 genome AF: 0.0000264 AC: 3AN: 113792Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 35906
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 12, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 02, 2020 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 30, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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 | Dec 11, 2023 | - - |
FLNA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 13, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at