3-13637835-C-G

Variant names:

• chr3-13637835-C-G
• rs1061376
• NM_001004019.2:c.3612C>G

Variant summary

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

The NM_001004019.2(FBLN2):​c.3612C>G​(p.Asp1204Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBLN2 NM_001004019.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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.3612C>G	p.Asp1204Glu	missense_variant	Exon 18 of 18	ENST00000404922.8	NP_001004019.1
FBLN2	NM_001165035.2	c.3612C>G	p.Asp1204Glu	missense_variant	Exon 18 of 18		NP_001158507.1
FBLN2	NM_001998.3	c.3471C>G	p.Asp1157Glu	missense_variant	Exon 17 of 17		NP_001989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBLN2	ENST00000404922.8	c.3612C>G	p.Asp1204Glu	missense_variant	Exon 18 of 18	5	NM_001004019.2	ENSP00000384169.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;.
Eigen	Benign	-0.045
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.79	.;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.54
Sift	Benign	0.19	T;T;T
Sift4G	Uncertain	0.022	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.36
MVP		0.60
MPC		0.23
ClinPred		0.96	D
GERP RS		-1.8
Varity_R		0.090
gMVP		0.64

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: rs1061376; hg19: chr3-13679335;