5-128335997-C-G

Variant names:

• chr5-128335997-C-G
• rs778784375
• NM_001999.4:c.3715G>C

Variant summary

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

The NM_001999.4(FBN2):​c.3715G>C​(p.Gly1239Arg) 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: 32)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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.3715G>C	p.Gly1239Arg	missense_variant	Exon 28 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.3562G>C	p.Gly1188Arg	missense_variant	Exon 27 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.3715G>C	p.Gly1239Arg	missense_variant	Exon 28 of 65	1	NM_001999.4	ENSP00000262464.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	T;.;T;D;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.;.;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	1.2	L;.;L;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.9	D;.;D;D;D
REVEL	Uncertain	0.63
Sift	Benign	0.28	T;.;T;T;T
Sift4G	Benign	0.32	.;.;.;T;T
Polyphen		0.95	P;.;P;.;P
Vest4		0.77
MutPred		0.44		Gain of solvent accessibility (P = 0.0789);.;Gain of solvent accessibility (P = 0.0789);.;.;
MVP		0.70
MPC		0.53
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.33
gMVP		0.81

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: rs778784375; hg19: chr5-127671689;