GeneBe

X-154348764-C-CCG

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000490936.5(FLNA):​n.5257_5258insCG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

FLNA
ENST00000490936.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.718

Publications

1 publications found
Variant links:
Genes affected
FLNA (HGNC:3754): (filamin A) The protein encoded by this gene is an actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins. The encoded protein is involved in remodeling the cytoskeleton to effect changes in cell shape and migration. This protein interacts with integrins, transmembrane receptor complexes, and second messengers. Defects in this gene are a cause of several syndromes, including periventricular nodular heterotopias (PVNH1, PVNH4), otopalatodigital syndromes (OPD1, OPD2), frontometaphyseal dysplasia (FMD), Melnick-Needles syndrome (MNS), and X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]
FLNA Gene-Disease associations (from GenCC):
  • periventricular nodular heterotopia
    Inheritance: AD, XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
  • frontometaphyseal dysplasia 1
    Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
  • genetic developmental and epileptic encephalopathy
    Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
  • heterotopia, periventricular, X-linked dominant
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
  • intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • Melnick-Needles syndrome
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
  • otopalatodigital syndrome type 2
    Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
  • terminal osseous dysplasia-pigmentary defects syndrome
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
  • cardiac valvular dysplasia, X-linked
    Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • frontometaphyseal dysplasia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • congenital short bowel syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • otopalatodigital syndrome type 1
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • X-linked Ehlers-Danlos syndrome
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • familial thoracic aortic aneurysm and aortic dissection
    Inheritance: XL Classification: LIMITED Submitted by: ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLNANM_001110556.2 linkc.*84_*85insCG 3_prime_UTR_variant Exon 48 of 48 ENST00000369850.10 NP_001104026.1 P21333-1Q60FE5Q6NXF2
FLNANM_001456.4 linkc.*84_*85insCG 3_prime_UTR_variant Exon 47 of 47 NP_001447.2 P21333-2Q60FE5Q6NXF2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLNAENST00000369850.10 linkc.*84_*85insCG 3_prime_UTR_variant Exon 48 of 48 1 NM_001110556.2 ENSP00000358866.3 P21333-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
873866
Hom.:
0
Cov.:
14
AF XY:
0.00
AC XY:
0
AN XY:
242852
African (AFR)
AF:
0.00
AC:
0
AN:
21118
American (AMR)
AF:
0.00
AC:
0
AN:
24153
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14332
East Asian (EAS)
AF:
0.00
AC:
0
AN:
26844
South Asian (SAS)
AF:
0.00
AC:
0
AN:
41446
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
32963
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3139
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
671927
Other (OTH)
AF:
0.00
AC:
0
AN:
37944
GnomAD4 genome
Cov.:
24
Alfa
AF:
0.00
Hom.:
146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs201431046; hg19: chrX-153577132; API