3-13570765-T-G

Position:

• chr3-13570765-T-G

Variant summary

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

The NM_001004019.2(FBLN2):​c.410T>G​(p.Val137Gly) 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: 6.14

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/exons	MANE	UniProt
FBLN2	NM_001004019.2	c.410T>G	p.Val137Gly	missense_variant	2/18	ENST00000404922.8
FBLN2	NM_001165035.2	c.410T>G	p.Val137Gly	missense_variant	2/18
FBLN2	NM_001998.3	c.410T>G	p.Val137Gly	missense_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN2	ENST00000404922.8	c.410T>G	p.Val137Gly	missense_variant	2/18	5	NM_001004019.2	P1
FBLN2	ENST00000295760.11	c.410T>G	p.Val137Gly	missense_variant	2/17	1
FBLN2	ENST00000492059.5	c.410T>G	p.Val137Gly	missense_variant	2/18	2		P1
FBLN2	ENST00000465610.1	c.410T>G	p.Val137Gly	missense_variant	2/2	2

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.410T>G (p.V137G) alteration is located in exon 2 (coding exon 1) of the FBLN2 gene. This alteration results from a T to G substitution at nucleotide position 410, causing the valine (V) at amino acid position 137 to be replaced by a glycine (G). 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	0.20
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.2	M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.98	D;D;.;D
Vest4		0.52
MVP		0.47
MPC		0.49
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.77
gMVP		0.70

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: chr3-13612265;