rs34845843

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001999.4(FBN2):​c.6253C>T​(p.Pro2085Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FBN2
NM_001999.4 missense

Scores

9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBN2NM_001999.4 linkc.6253C>T p.Pro2085Ser missense_variant Exon 49 of 65 ENST00000262464.9 NP_001990.2 P35556-1
FBN2XM_017009228.3 linkc.6100C>T p.Pro2034Ser missense_variant Exon 48 of 64 XP_016864717.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBN2ENST00000262464.9 linkc.6253C>T p.Pro2085Ser missense_variant Exon 49 of 65 1 NM_001999.4 ENSP00000262464.4 P35556-1
FBN2ENST00000703783.1 linkn.3037C>T non_coding_transcript_exon_variant Exon 24 of 38
FBN2ENST00000703785.1 linkn.2956C>T non_coding_transcript_exon_variant Exon 23 of 27

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Nov 16, 2021
Revvity Omics, Revvity
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.54
D;.;D
Eigen
Benign
-0.076
Eigen_PC
Benign
0.098
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.71
T;.;.
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.44
T;T;T
MetaSVM
Uncertain
0.12
D
MutationAssessor
Benign
0.25
N;.;N
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-2.6
D;.;D
REVEL
Uncertain
0.48
Sift
Benign
0.35
T;.;T
Polyphen
0.090
B;.;B
Vest4
0.39
MutPred
0.54
Loss of catalytic residue at P2084 (P = 0.0415);.;Loss of catalytic residue at P2084 (P = 0.0415);
MVP
0.58
MPC
0.79
ClinPred
0.98
D
GERP RS
4.4
Varity_R
0.13
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs34845843; hg19: chr5-127627260; COSMIC: COSV99325473; API