rs748419325
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP6
The NM_001999.4(FBN2):āc.1897A>Gā(p.Ile633Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,326 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000027 ( 1 hom. )
Consequence
FBN2
NM_001999.4 missense
NM_001999.4 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 6.18
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, FBN2
BP6
?
Variant 5-128376806-T-C is Benign according to our data. Variant chr5-128376806-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 547353.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.1897A>G | p.Ile633Val | missense_variant | 14/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.1744A>G | p.Ile582Val | missense_variant | 13/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.1897A>G | p.Ile633Val | missense_variant | 14/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000508989.5 | c.1798A>G | p.Ile600Val | missense_variant | 13/33 | 2 | |||
FBN2 | ENST00000511489.1 | n.118A>G | non_coding_transcript_exon_variant | 2/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251072Hom.: 1 AF XY: 0.00 AC XY: 0AN XY: 135684
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461326Hom.: 1 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726974
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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32
ExAC
?
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1
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Connective tissue disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Congenital contractural arachnodactyly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;.;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;.;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N
REVEL
Uncertain
Sift
Benign
T;.;T;T
Polyphen
P;.;P;P
Vest4
MutPred
Gain of catalytic residue at I633 (P = 0.0767);.;Gain of catalytic residue at I633 (P = 0.0767);.;
MVP
MPC
0.26
ClinPred
D
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