3-13629274-TTT-CTG

Variant names:

• chr3-13629274-TTT-CTG
• NM_001004019.2:c.2824_2826delTTTinsCTG
• FBLN2 p.Phe942Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001004019.2(FBLN2):​c.2824_2826delTTTinsCTG​(p.Phe942Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F942F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FBLN2 NM_001004019.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01
• Publications: 0 publications found

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]

FBLN2 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• pulmonary arterial hypertension

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004019.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLN2	NM_001004019.2	MANE Select	c.2824_2826delTTTinsCTG	p.Phe942Leu	missense	N/A	NP_001004019.1	P98095-2
	FBLN2	NM_001165035.2		c.2824_2826delTTTinsCTG	p.Phe942Leu	missense	N/A	NP_001158507.1	P98095-2
	FBLN2	NM_001998.3		c.2683_2685delTTTinsCTG	p.Phe895Leu	missense	N/A	NP_001989.2	P98095-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLN2	ENST00000404922.8	TSL:5 MANE Select	c.2824_2826delTTTinsCTG	p.Phe942Leu	missense	N/A	ENSP00000384169.3	P98095-2
	FBLN2	ENST00000295760.11	TSL:1	c.2683_2685delTTTinsCTG	p.Phe895Leu	missense	N/A	ENSP00000295760.7	P98095-1
	FBLN2	ENST00000492059.5	TSL:2	c.2824_2826delTTTinsCTG	p.Phe942Leu	missense	N/A	ENSP00000420042.1	P98095-2

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-13670774;