rs114376818

Variant names:

• chr5-128278717-C-G
• NM_001999.4:c.7263G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-128278717-C-G
• chr5-128278717-C-T

Variant summary

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

The NM_001999.4(FBN2):​c.7263G>C​(p.Gln2421His) 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 1,461,866 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: 0.145

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.7263G>C	p.Gln2421His	missense_variant	Exon 57 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.7110G>C	p.Gln2370His	missense_variant	Exon 56 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.7263G>C	p.Gln2421His	missense_variant	Exon 57 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000703783.1	n.4047G>C		non_coding_transcript_exon_variant	Exon 32 of 38

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.28	T;.;T
Eigen	Benign	0.0072
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.38	T;.;.
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	-0.030	T
MutationAssessor	Benign	0.53	N;.;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.49	N;.;N
REVEL	Uncertain	0.46
Sift	Benign	0.86	T;.;T
Polyphen		1.0	D;.;D
Vest4		0.58
MutPred		0.65		Loss of disorder (P = 0.2434);.;Loss of disorder (P = 0.2434);
MVP		0.69
MPC		0.25
ClinPred		0.69	D
GERP RS		2.0
Varity_R		0.055
gMVP		0.66

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: chr5-127614409;