5-128335211-T-G

Position:

• chr5-128335211-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001999.4(FBN2):​c.3932A>C​(p.Tyr1311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4	c.3932A>C	p.Tyr1311Ser	missense_variant	30/65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.3779A>C	p.Tyr1260Ser	missense_variant	29/64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.3932A>C	p.Tyr1311Ser	missense_variant	30/65	1	NM_001999.4	ENSP00000262464.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Uncertain	0.76	D;.;D;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	T;.;.;T;T
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	-0.70	N;.;N;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.4	D;.;D;D;D
REVEL	Uncertain	0.59
Sift	Benign	0.085	T;.;T;T;T
Sift4G	Benign	0.44	.;.;.;T;T
Polyphen		0.86	P;.;P;.;B
Vest4		0.76
MutPred		0.61		Gain of disorder (P = 0.018);.;Gain of disorder (P = 0.018);.;.;
MVP		0.93
MPC		0.38
ClinPred		0.88	D
GERP RS		5.1
Varity_R		0.43
gMVP		0.91

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: chr5-127670903;