3-13571436-A-T

Position:

• chr3-13571436-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004019.2(FBLN2):​c.1081A>T​(p.Ser361Cys) 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. 15/21 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. S361G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FBLN2 NM_001004019.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083384484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLN2	NM_001004019.2	c.1081A>T	p.Ser361Cys	missense_variant	2/18	ENST00000404922.8	NP_001004019.1
FBLN2	NM_001165035.2	c.1081A>T	p.Ser361Cys	missense_variant	2/18		NP_001158507.1
FBLN2	NM_001998.3	c.1081A>T	p.Ser361Cys	missense_variant	2/17		NP_001989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLN2	ENST00000404922.8	c.1081A>T	p.Ser361Cys	missense_variant	2/18	5	NM_001004019.2	ENSP00000384169.3
FBLN2	ENST00000295760.11	c.1081A>T	p.Ser361Cys	missense_variant	2/17	1		ENSP00000295760.7
FBLN2	ENST00000492059.5	c.1081A>T	p.Ser361Cys	missense_variant	2/18	2		ENSP00000420042.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.80
DEOGEN2	Benign	0.13	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.36	.;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.047	D;D;D
Sift4G	Uncertain	0.041	D;D;D
Polyphen		0.20	B;B;B
Vest4		0.10
MVP		0.30
MPC		0.24
ClinPred		0.17	T
GERP RS		1.9
Varity_R		0.078
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

Other links and lift over

dbSNP: rs3732666; hg19: chr3-13612936;