rs1297639505

Variant names:

• chr5-128357330-T-A
• rs1297639505
• NM_001999.4:c.2620A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-128357330-T-A
• chr5-128357330-T-C
• chr5-128357330-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.2620A>T​(p.Asn874Tyr) 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. 16/21 in silico tools predict 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)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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=0.25626922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.2620A>T	p.Asn874Tyr	missense_variant	Exon 20 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.2467A>T	p.Asn823Tyr	missense_variant	Exon 19 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.2620A>T	p.Asn874Tyr	missense_variant	Exon 20 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000508989.5	c.2521A>T	p.Asn841Tyr	missense_variant	Exon 19 of 33	2		ENSP00000425596.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	9.1
DANN	Benign	0.93
DEOGEN2	Benign	0.34	T;.;T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.81	T;.;.;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	-0.14	N;.;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.98	N;.;N;N
REVEL	Benign	0.23
Sift	Benign	0.53	T;.;T;T
Sift4G	Benign	0.27	.;.;.;T
Polyphen		0.0	B;.;B;B
Vest4		0.45
MutPred		0.51		Loss of disorder (P = 0.0056);.;Loss of disorder (P = 0.0056);.;
MVP		0.19
MPC		0.37
ClinPred		0.41	T
GERP RS		2.6
Varity_R		0.049
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs1297639505; hg19: chr5-127693022;