rs863223562

Variant names:

• chr5-128344475-T-C
• NM_001999.4:c.3253A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-128344475-T-C
• chr5-128344475-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001999.4(FBN2):​c.3253A>G​(p.Thr1085Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 0.0000014 (0 hom.)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31951562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.3253A>G	p.Thr1085Ala	missense_variant	Exon 25 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.3100A>G	p.Thr1034Ala	missense_variant	Exon 24 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.3253A>G	p.Thr1085Ala	missense_variant	Exon 25 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000508989.5	c.3154A>G	p.Thr1052Ala	missense_variant	Exon 24 of 33	2		ENSP00000425596.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461272 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726986

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: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Uncertain	0.50	T;.;T;D
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	T;.;.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	0.12	N;.;N;.
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	N;.;N;N
REVEL	Uncertain	0.54
Sift	Benign	0.20	T;.;T;T
Sift4G	Benign	0.68	.;.;.;T
Polyphen		0.071	B;.;B;B
Vest4		0.30
MutPred		0.48		Loss of ubiquitination at K1088 (P = 0.1264);.;Loss of ubiquitination at K1088 (P = 0.1264);.;
MVP		0.88
MPC		0.25
ClinPred		0.41	T
GERP RS		4.3
Varity_R		0.089
gMVP		0.54

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: chr5-127680167;