rs1060503511

Variant names:

• chr5-128330633-G-C
• NM_001999.4:c.4285C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-128330633-G-C
• chr5-128330633-G-T

Variant summary

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

The NM_001999.4(FBN2):​c.4285C>G​(p.Pro1429Ala) 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 1,461,658 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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.4285C>G	p.Pro1429Ala	missense_variant	Exon 33 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.4132C>G	p.Pro1378Ala	missense_variant	Exon 32 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.4285C>G	p.Pro1429Ala	missense_variant	Exon 33 of 65	1	NM_001999.4	ENSP00000262464.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461658 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727132

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: 8.99e-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	0.079
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Benign	0.65
DEOGEN2	Uncertain	0.65	D;.;D;D;D
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;.;.;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.62	D;D;D;D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.3	L;.;L;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.0	D;.;D;D;D
REVEL	Pathogenic	0.65
Sift	Benign	0.25	T;.;T;T;T
Sift4G	Benign	0.74	.;.;.;T;T
Polyphen		0.80	P;.;P;.;P
Vest4		0.52
MutPred		0.50		Gain of catalytic residue at P1429 (P = 0.0026);.;Gain of catalytic residue at P1429 (P = 0.0026);.;.;
MVP		0.65
MPC		0.85
ClinPred		0.90	D
GERP RS		4.2
Varity_R		0.098
gMVP		0.75

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: chr5-127666325;