rs797045573

Variant names:

• chr5-128328706-T-A
• rs797045573
• NM_001999.4:c.4461A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-128328706-T-A
• chr5-128328706-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001999.4(FBN2):​c.4461A>T​(p.Arg1487Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.566

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17827022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.4461A>T	p.Arg1487Ser	missense_variant	Exon 34 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.4308A>T	p.Arg1436Ser	missense_variant	Exon 33 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.4461A>T	p.Arg1487Ser	missense_variant	Exon 34 of 65	1	NM_001999.4	ENSP00000262464.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461818 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 01, 2014

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.64	D;.;D;D;D
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.84	T;.;.;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	1.5	L;.;L;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.3	D;.;D;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.013	D;.;D;D;D
Sift4G	Benign	0.54	.;.;.;T;T
Polyphen		0.037	B;.;B;.;D
Vest4		0.46
MutPred		0.41		Loss of catalytic residue at R1487 (P = 0.0099);.;Loss of catalytic residue at R1487 (P = 0.0099);.;.;
MVP		0.46
MPC		0.42
ClinPred		0.97	D
GERP RS		-4.6
Varity_R		0.33
gMVP		0.82

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: rs797045573; hg19: chr5-127664398;