rs154001

Variant names:

• chr5-128349443-C-G
• rs154001
• NM_001999.4:c.2893G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-128349443-C-G
• chr5-128349443-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001999.4(FBN2):​c.2893G>C​(p.Val965Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V965I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11

Genes affected

FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.2893G>C	p.Val965Leu	missense_variant	Exon 23 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.2740G>C	p.Val914Leu	missense_variant	Exon 22 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.2893G>C	p.Val965Leu	missense_variant	Exon 23 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000508989.5	c.2794G>C	p.Val932Leu	missense_variant	Exon 22 of 33	2		ENSP00000425596.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;.;T;T
Eigen	Benign	0.031
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T;.;.;T
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	-0.21	N;.;N;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	N;.;N;N
REVEL	Uncertain	0.58
Sift	Benign	0.17	T;.;T;T
Sift4G	Benign	0.43	.;.;.;T
Polyphen		0.12	B;.;B;P
Vest4		0.67
MutPred		0.48		Loss of disorder (P = 0.2389);.;Loss of disorder (P = 0.2389);.;
MVP		0.83
MPC		0.38
ClinPred		0.89	D
GERP RS		3.3
Varity_R		0.24
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: rs154001; hg19: chr5-127685135;