5-128263449-G-C

Variant names:

• chr5-128263449-G-C
• NM_001999.4:c.8168C>G

Variant summary

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

The NM_001999.4(FBN2):​c.8168C>G​(p.Pro2723Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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.8168C>G	p.Pro2723Arg	missense_variant	Exon 63 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.8015C>G	p.Pro2672Arg	missense_variant	Exon 62 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.8168C>G	p.Pro2723Arg	missense_variant	Exon 63 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000703782.1	n.283C>G		non_coding_transcript_exon_variant	Exon 2 of 2
FBN2	ENST00000703783.1	n.*179C>G		downstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461386 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727046

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Uncertain	0.72	D;.;D
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.68	T;.;.
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Benign	0.83	L;.;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.6	D;.;D
REVEL	Uncertain	0.54
Sift	Benign	0.24	T;.;T
Polyphen		0.98	D;.;D
Vest4		0.69
MutPred		0.59		Gain of sheet (P = 0.0266);.;Gain of sheet (P = 0.0266);
MVP		0.59
MPC		0.26
ClinPred		0.85	D
GERP RS		5.2
Varity_R		0.18
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: 1

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: chr5-127599141;