rs143796236
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_012418.4(FSCN2):c.412C>T(p.His138Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 1,590,356 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0061 ( 4 hom., cov: 34)
Exomes 𝑓: 0.0078 ( 56 hom. )
Consequence
FSCN2
NM_012418.4 missense
NM_012418.4 missense
Scores
3
11
4
Clinical Significance
Conservation
PhyloP100: 7.29
Genes affected
FSCN2 (HGNC:3960): (fascin actin-bundling protein 2, retinal) This gene encodes a member of the fascin protein family. Fascins crosslink actin into filamentous bundles within dynamic cell extensions. This family member is proposed to play a role in photoreceptor disk morphogenesis. A mutation in this gene results in one form of autosomal dominant retinitis pigmentosa and macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010590553).
BP6
?
Variant 17-81528943-C-T is Benign according to our data. Variant chr17-81528943-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 167106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81528943-C-T is described in Lovd as [Benign].
BS2
?
High AC in GnomAd4 at 925 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FSCN2 | NM_012418.4 | c.412C>T | p.His138Tyr | missense_variant | 1/5 | ENST00000417245.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FSCN2 | ENST00000417245.7 | c.412C>T | p.His138Tyr | missense_variant | 1/5 | 1 | NM_012418.4 | P1 | |
FSCN2 | ENST00000334850.7 | c.412C>T | p.His138Tyr | missense_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00606 AC: 923AN: 152248Hom.: 4 Cov.: 34
GnomAD3 genomes
?
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923
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34
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GnomAD3 exomes AF: 0.00714 AC: 1485AN: 208014Hom.: 10 AF XY: 0.00721 AC XY: 831AN XY: 115226
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GnomAD4 exome AF: 0.00776 AC: 11157AN: 1437990Hom.: 56 Cov.: 33 AF XY: 0.00781 AC XY: 5577AN XY: 714244
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GnomAD4 genome ? AF: 0.00607 AC: 925AN: 152366Hom.: 4 Cov.: 34 AF XY: 0.00608 AC XY: 453AN XY: 74510
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ESP6500AA
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ExAC
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Asia WGS
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3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | FSCN2: BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 10, 2017 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 23, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
0.45
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at