5-128393177-C-A

Variant names:

• chr5-128393177-C-A
• rs200440156
• NM_001999.4:c.1423G>T

Variant summary

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

The NM_001999.4(FBN2):​c.1423G>T​(p.Gly475Cys) 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: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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 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
FBN2	NM_001999.4	c.1423G>T	p.Gly475Cys	missense_variant	Exon 10 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.1270G>T	p.Gly424Cys	missense_variant	Exon 9 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.1423G>T	p.Gly475Cys	missense_variant	Exon 10 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000508989.5	c.1324G>T	p.Gly442Cys	missense_variant	Exon 9 of 33	2		ENSP00000425596.1
FBN2	ENST00000703787.1	n.1130G>T		non_coding_transcript_exon_variant	Exon 9 of 10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.84	T;.;.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.1	M;.;M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.5	N;.;N;N
REVEL	Uncertain	0.53
Sift	Benign	0.098	T;.;T;T
Sift4G	Benign	0.13	.;.;.;T
Polyphen		1.0	D;.;D;D
Vest4		0.63
MutPred		0.52		Loss of disorder (P = 0.0106);.;Loss of disorder (P = 0.0106);.;
MVP		0.65
MPC		0.85
ClinPred		0.74	D
GERP RS		3.2
Varity_R		0.085
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200440156; hg19: chr5-127728870;