5-157285452-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001037333.3(CYFIP2):c.91C>T(p.Pro31Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,540 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
CYFIP2
NM_001037333.3 missense
NM_001037333.3 missense
Scores
6
3
7
Clinical Significance
Conservation
PhyloP100: 7.71
Genes affected
CYFIP2 (HGNC:13760): (cytoplasmic FMR1 interacting protein 2) Predicted to enable small GTPase binding activity. Involved in activation of cysteine-type endopeptidase activity; apoptotic process; and cell-cell adhesion. Located in perinuclear region of cytoplasm and synapse. Part of SCAR complex. Implicated in developmental and epileptic encephalopathy 65. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, CYFIP2
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYFIP2 | NM_001037333.3 | c.91C>T | p.Pro31Ser | missense_variant | 2/31 | ENST00000620254.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYFIP2 | ENST00000620254.5 | c.91C>T | p.Pro31Ser | missense_variant | 2/31 | 1 | NM_001037333.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000538 AC: 1AN: 185714Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 98556
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GnomAD4 exome AF: 7.04e-7 AC: 1AN: 1420540Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 702478
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 31, 2022 | This variant has not been reported in the literature in individuals affected with CYFIP2-related conditions. 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. 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: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 31 of the CYFIP2 protein (p.Pro31Ser). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T;.;.;T;T;T;.;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.;.;.;.;.;L
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
D;P;P;.;P;.;.;.;P
Vest4
MutPred
Loss of catalytic residue at P31 (P = 0.0362);Loss of catalytic residue at P31 (P = 0.0362);Loss of catalytic residue at P31 (P = 0.0362);Loss of catalytic residue at P31 (P = 0.0362);Loss of catalytic residue at P31 (P = 0.0362);Loss of catalytic residue at P31 (P = 0.0362);Loss of catalytic residue at P31 (P = 0.0362);Loss of catalytic residue at P31 (P = 0.0362);Loss of catalytic residue at P31 (P = 0.0362);
MVP
MPC
1.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at