dbSNP rs777965029: FBLN2:p.Thr34Arg (chr3-13570456-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001004019.2(FBLN2):c.101C>G(p.Thr34Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,419,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T34M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

FBLN2
NM_001004019.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.47

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.101C>G	p.Thr34Arg	missense	Exon 2 of 18	NP_001004019.1	P98095-2
FBLN2	NM_001165035.2		c.101C>G	p.Thr34Arg	missense	Exon 2 of 18	NP_001158507.1	P98095-2
FBLN2	NM_001998.3		c.101C>G	p.Thr34Arg	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.101C>G	p.Thr34Arg	missense	Exon 2 of 18	ENSP00000384169.3	P98095-2
FBLN2	ENST00000295760.11	TSL:1	c.101C>G	p.Thr34Arg	missense	Exon 2 of 17	ENSP00000295760.7	P98095-1
FBLN2	ENST00000492059.5	TSL:2	c.101C>G	p.Thr34Arg	missense	Exon 2 of 18	ENSP00000420042.1	P98095-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1419572

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702050

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32690

American (AMR)

AF:

0.00

AC:

AN:

39154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25414

East Asian (EAS)

AF:

0.00

AC:

AN:

37530

South Asian (SAS)

AF:

0.00

AC:

AN:

81046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1092056

Other (OTH)

AF:

0.00

AC:

AN:

58668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

PhyloP100

7.5

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.71

MVP

0.42

MPC

0.61

ClinPred

0.99

GERP RS

5.0

Varity_R

0.66

gMVP

0.79

Mutation Taster

=28/72

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over