rs368116715

Variant names:

• chr5-128364665-C-G
• NM_001999.4:c.2363G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-128364665-C-G
• chr5-128364665-C-T

Variant summary

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

The NM_001999.4(FBN2):​c.2363G>C​(p.Arg788Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R788H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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.2363G>C	p.Arg788Pro	missense_variant	Exon 18 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.2210G>C	p.Arg737Pro	missense_variant	Exon 17 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.2363G>C	p.Arg788Pro	missense_variant	Exon 18 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000508989.5	c.2264G>C	p.Arg755Pro	missense_variant	Exon 17 of 33	2		ENSP00000425596.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460850 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726814

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.;D;D
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.92	D;.;.;D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Uncertain	-0.039	T
MutationAssessor	Benign	-1.7	N;.;N;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.5	D;.;D;D
REVEL	Pathogenic	0.66
Sift	Benign	0.046	D;.;D;T
Sift4G	Benign	0.31	.;.;.;T
Polyphen		0.93	P;.;P;D
Vest4		0.66
MutPred		0.55		Gain of catalytic residue at N786 (P = 0.0743);.;Gain of catalytic residue at N786 (P = 0.0743);.;
MVP		0.89
MPC		0.95
ClinPred		0.98	D
GERP RS		2.6
Varity_R		0.74
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-127700358;