rs1554123061

Variant names:

• chr5-128338078-T-A
• rs1554123061
• NM_001999.4:c.3517A>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001999.4(FBN2):​c.3517A>T​(p.Thr1173Ser) 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 benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.407

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30751163).
• BP6: Variant 5-128338078-T-A is Benign according to our data. Variant chr5-128338078-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 547357.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.3517A>T	p.Thr1173Ser	missense_variant	Exon 27 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.3364A>T	p.Thr1122Ser	missense_variant	Exon 26 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.3517A>T	p.Thr1173Ser	missense_variant	Exon 27 of 65	1	NM_001999.4	ENSP00000262464.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Connective tissue disorder Benign:1

Nov 01, 2016

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T;.;T;T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.67	T;.;.;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	0.55	N;.;N;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N;.;N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.19	T;.;T;T;T
Sift4G	Benign	0.23	.;.;.;T;T
Polyphen		0.037	B;.;B;.;B
Vest4		0.24
MutPred		0.64		Gain of disorder (P = 0.065);.;Gain of disorder (P = 0.065);.;.;
MVP		0.46
MPC		0.30
ClinPred		0.36	T
GERP RS		4.3
Varity_R		0.085
gMVP		0.48

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: rs1554123061; hg19: chr5-127673770;