Variant chr5-128349443-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3

The ENST00000262464.9(FBN2):c.2893G>C(p.Val965Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V965I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

FBN2
ENST00000262464.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.11

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]

FBN2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), FBN2. . Gene score misZ 1.5491 (greater than the threshold 3.09). Trascript score misZ 3.2752 (greater than threshold 3.09). GenCC has associacion of gene with familial thoracic aortic aneurysm and aortic dissection, carpal tunnel syndrome, macular degeneration, early-onset, congenital contractural arachnodactyly.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4 linkuse as main transcript	c.2893G>C	p.Val965Leu	missense_variant	23/65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3 linkuse as main transcript	c.2740G>C	p.Val914Leu	missense_variant	22/64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.2893G>C	p.Val965Leu	missense_variant	23/65	1	NM_001999.4	ENSP00000262464	P1	P35556-1
FBN2	ENST00000508989.5 linkuse as main transcript	c.2794G>C	p.Val932Leu	missense_variant	22/33	2		ENSP00000425596

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

T;.;T;T

Eigen

Benign

0.031

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

T;.;.;T

M_CAP

Benign

0.079

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Uncertain

0.50

MutationAssessor

Benign

-0.21

N;.;N;.

MutationTaster

Benign

0.013

P;P;P

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.7

N;.;N;N

REVEL

Uncertain

0.58

Sift

Benign

0.17

T;.;T;T

Sift4G

Benign

0.43

.;.;.;T

Polyphen

0.12

B;.;B;P

Vest4

0.67

MutPred

0.48

Loss of disorder (P = 0.2389);.;Loss of disorder (P = 0.2389);.;

MVP

0.83

MPC

0.38

ClinPred

0.89

GERP RS

3.3

Varity_R

0.24

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over