rs193920763
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001999.4(FBN2):c.6177A>C(p.Glu2059Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
FBN2
NM_001999.4 missense
NM_001999.4 missense
Scores
8
9
1
Clinical Significance
Conservation
PhyloP100: 0.203
Genes affected
FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, FBN2
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.885
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.6177A>C | p.Glu2059Asp | missense_variant | 49/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.6024A>C | p.Glu2008Asp | missense_variant | 48/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.6177A>C | p.Glu2059Asp | missense_variant | 49/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000703783.1 | n.2961A>C | non_coding_transcript_exon_variant | 24/38 | |||||
FBN2 | ENST00000703785.1 | n.2880A>C | non_coding_transcript_exon_variant | 23/27 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D
REVEL
Pathogenic
Sift
Pathogenic
D;.;D
Polyphen
D;.;D
Vest4
MutPred
Loss of disorder (P = 0.2111);.;Loss of disorder (P = 0.2111);
MVP
MPC
0.82
ClinPred
D
GERP RS
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