chr3-13570707-C-G

Variant names:

• chr3-13570707-C-G
• NM_001004019.2:c.352C>G

Variant summary

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

The NM_001004019.2(FBLN2):​c.352C>G​(p.Pro118Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: FBLN2 NM_001004019.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07

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]

ACMG classification

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
FBLN2	NM_001004019.2	c.352C>G	p.Pro118Ala	missense_variant	Exon 2 of 18	ENST00000404922.8	NP_001004019.1
FBLN2	NM_001165035.2	c.352C>G	p.Pro118Ala	missense_variant	Exon 2 of 18		NP_001158507.1
FBLN2	NM_001998.3	c.352C>G	p.Pro118Ala	missense_variant	Exon 2 of 17		NP_001989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBLN2	ENST00000404922.8	c.352C>G	p.Pro118Ala	missense_variant	Exon 2 of 18	5	NM_001004019.2	ENSP00000384169.3
FBLN2	ENST00000295760.11	c.352C>G	p.Pro118Ala	missense_variant	Exon 2 of 17	1		ENSP00000295760.7
FBLN2	ENST00000492059.5	c.352C>G	p.Pro118Ala	missense_variant	Exon 2 of 18	2		ENSP00000420042.1
FBLN2	ENST00000465610.1	c.352C>G	p.Pro118Ala	missense_variant	Exon 2 of 2	2		ENSP00000420164.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.352C>G (p.P118A) alteration is located in exon 2 (coding exon 1) of the FBLN2 gene. This alteration results from a C to G substitution at nucleotide position 352, causing the proline (P) at amino acid position 118 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	.;D;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	.;D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.5	M;M;.;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.52
MVP		0.61
MPC		0.17
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-13612207;