rs376194507

Variant names:

• chr5-128350879-C-A
• NM_001999.4:c.2801G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-128350879-C-A
• chr5-128350879-C-G
• chr5-128350879-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001999.4(FBN2):​c.2801G>T​(p.Arg934Leu) 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 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.208

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.2801G>T	p.Arg934Leu	missense_variant	Exon 21 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.2648G>T	p.Arg883Leu	missense_variant	Exon 20 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.2801G>T	p.Arg934Leu	missense_variant	Exon 21 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000508989.5	c.2702G>T	p.Arg901Leu	missense_variant	Exon 20 of 33	2		ENSP00000425596.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.14
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	26
DANN	Benign	0.91
DEOGEN2	Uncertain	0.52	D;.;D;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.88	D;.;.;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	0.84	L;.;L;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N;.;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.30	T;.;T;T
Sift4G	Benign	0.41	.;.;.;T
Polyphen		0.64	P;.;P;B
Vest4		0.38
MutPred		0.54		Loss of disorder (P = 0.0849);.;Loss of disorder (P = 0.0849);.;
MVP		0.58
MPC		0.32
ClinPred		0.27	T
GERP RS		3.7
Varity_R		0.14
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-127686571; COSMIC: COSV99325806;