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GeneBe

rs797045573

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001999.4(FBN2):c.4461A>T(p.Arg1487Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FBN2
NM_001999.4 missense

Scores

9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.566
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, FBN2
BP4
Computational evidence support a benign effect (MetaRNN=0.17827022).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FBN2NM_001999.4 linkuse as main transcriptc.4461A>T p.Arg1487Ser missense_variant 34/65 ENST00000262464.9
FBN2XM_017009228.3 linkuse as main transcriptc.4308A>T p.Arg1436Ser missense_variant 33/64

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FBN2ENST00000262464.9 linkuse as main transcriptc.4461A>T p.Arg1487Ser missense_variant 34/651 NM_001999.4 P1P35556-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461818
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoDec 01, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.062
T
BayesDel_noAF
Benign
-0.15
Cadd
Benign
16
Dann
Uncertain
0.98
DEOGEN2
Uncertain
0.64
D;.;D;D;D
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.84
T;.;.;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.18
T;T;T;T;T
MetaSVM
Uncertain
0.30
D
MutationAssessor
Benign
1.5
L;.;L;.;.
MutationTaster
Benign
0.99
D;N;N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-3.3
D;.;D;D;D
REVEL
Uncertain
0.50
Sift
Uncertain
0.013
D;.;D;D;D
Polyphen
0.037
B;.;B;.;D
Vest4
0.46
MutPred
0.41
Loss of catalytic residue at R1487 (P = 0.0099);.;Loss of catalytic residue at R1487 (P = 0.0099);.;.;
MVP
0.46
MPC
0.42
ClinPred
0.97
D
GERP RS
-4.6
Varity_R
0.33
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs797045573; hg19: chr5-127664398; API