rs143722436

Variant names:

• chr5-128374639-C-A
• NM_001999.4:c.2084G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-128374639-C-A
• chr5-128374639-C-G
• chr5-128374639-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001999.4(FBN2):​c.2084G>T​(p.Arg695Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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: 7.91

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.2084G>T	p.Arg695Leu	missense_variant	Exon 15 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.1931G>T	p.Arg644Leu	missense_variant	Exon 14 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.2084G>T	p.Arg695Leu	missense_variant	Exon 15 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000508989.5	c.1985G>T	p.Arg662Leu	missense_variant	Exon 14 of 33	2		ENSP00000425596.1
FBN2	ENST00000511489.1	n.305G>T		non_coding_transcript_exon_variant	Exon 3 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461668 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727140

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;.;D;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;.;.;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.89	D;D;D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Benign	1.5	L;.;L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.1	D;.;D;D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0020	D;.;D;T
Sift4G	Uncertain	0.048	.;.;.;D
Polyphen		1.0	D;.;D;D
Vest4		0.93
MutPred		0.65		Loss of disorder (P = 0.1415);.;Loss of disorder (P = 0.1415);.;
MVP		0.95
MPC		0.96
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.63
gMVP		0.77

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: chr5-127710332;