rs371611462
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_ModerateBP6_Very_Strong
The NM_001110556.2(FLNA):c.6220G>A(p.Asp2074Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000686 in 1,209,293 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. D2074D) 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.6220G>A | p.Asp2074Asn | missense_variant | 38/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.6196G>A | p.Asp2066Asn | missense_variant | 37/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.6220G>A | p.Asp2074Asn | missense_variant | 38/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000266 AC: 3AN: 112595Hom.: 0 Cov.: 26 AF XY: 0.0000288 AC XY: 1AN XY: 34757
GnomAD3 exomes AF: 0.0000387 AC: 7AN: 180894Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67192
GnomAD4 exome AF: 0.0000729 AC: 80AN: 1096698Hom.: 0 Cov.: 32 AF XY: 0.0000745 AC XY: 27AN XY: 362376
GnomAD4 genome ? AF: 0.0000266 AC: 3AN: 112595Hom.: 0 Cov.: 26 AF XY: 0.0000288 AC XY: 1AN XY: 34757
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 26, 2024 | Variant summary: FLNA c.6220G>A (p.Asp2074Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.9e-05 in 1209293 control chromosomes including 28 hemizygotes (gnomAD v4.0.0). The observed variant frequency is approximately 200 fold of the estimated maximal expected allele frequency for a pathogenic variant in FLNA causing Periventricular Nodular Heterotopia phenotype (3.1e-07), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.6220G>A in individuals affected with Periventricular Nodular Heterotopia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 533579). Based on the evidence outlined above, the variant was classified as likely benign. - |
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 | Jan 29, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 24, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at