Genetic Variant NM_001004019.2:c.116C>A (chr3-13570471-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004019.2(FBLN2):c.116C>A(p.Pro39Gln) 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 benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P39L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FBLN2
NM_001004019.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.98

Publications

0 publications found

Variant links:

Genes affected

FBLN2 (HGNC:3601): (fibulin 2) This gene encodes an extracellular matrix protein, which belongs to the fibulin family. This protein binds various extracellular ligands and calcium. It may play a role during organ development, in particular, during the differentiation of heart, skeletal and neuronal structures. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FBLN2 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
pulmonary arterial hypertension
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

FBLN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24295971).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004019.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBLN2	NM_001004019.2	MANE Select	c.116C>A	p.Pro39Gln	missense	Exon 2 of 18	NP_001004019.1	P98095-2
FBLN2	NM_001165035.2		c.116C>A	p.Pro39Gln	missense	Exon 2 of 18	NP_001158507.1	P98095-2
FBLN2	NM_001998.3		c.116C>A	p.Pro39Gln	missense	Exon 2 of 17	NP_001989.2	P98095-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBLN2	ENST00000404922.8	TSL:5 MANE Select	c.116C>A	p.Pro39Gln	missense	Exon 2 of 18	ENSP00000384169.3	P98095-2
FBLN2	ENST00000295760.11	TSL:1	c.116C>A	p.Pro39Gln	missense	Exon 2 of 17	ENSP00000295760.7	P98095-1
FBLN2	ENST00000492059.5	TSL:2	c.116C>A	p.Pro39Gln	missense	Exon 2 of 18	ENSP00000420042.1	P98095-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1425108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704940

African (AFR)

AF:

0.00

AC:

AN:

32788

American (AMR)

AF:

0.00

AC:

AN:

40116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

37802

South Asian (SAS)

AF:

0.00

AC:

AN:

81444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094778

Other (OTH)

AF:

0.00

AC:

AN:

58888

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.15

Eigen

Benign

0.12

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.80

M_CAP

Benign

0.011

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.2

PhyloP100

3.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.1

REVEL

Benign

0.043

Sift

Benign

0.20

Sift4G

Benign

0.28

Polyphen

0.94

Vest4

0.27

MVP

0.31

MPC

0.50

ClinPred

0.73

GERP RS

4.1

Varity_R

0.061

gMVP

0.66

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over