rs181420326

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012418.4(FSCN2):c.829G>A(p.Val277Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,528,232 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V277F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

FSCN2
NM_012418.4 missense, splice_region

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: 0.136

Publications

1 publications found

Variant links:

Genes affected

FSCN2 (HGNC:3960): (fascin actin-bundling protein 2, retinal) This gene encodes a member of the fascin protein family. Fascins crosslink actin into filamentous bundles within dynamic cell extensions. This family member is proposed to play a role in photoreceptor disk morphogenesis. A mutation in this gene results in one form of autosomal dominant retinitis pigmentosa and macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

FSCN2 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa 30
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

FSCN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013618946).

BS2

High AC in GnomAd4 at 115 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012418.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCN2	NM_012418.4	MANE Select	c.829G>A	p.Val277Ile	missense splice_region	Exon 2 of 5	NP_036550.1	O14926-1
	FSCN2	NM_001077182.3		c.829G>A	p.Val277Ile	missense splice_region	Exon 2 of 5	NP_001070650.1	O14926-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCN2	ENST00000417245.7	TSL:1 MANE Select	c.829G>A	p.Val277Ile	missense splice_region	Exon 2 of 5	ENSP00000388716.2	O14926-1
	FSCN2	ENST00000334850.7	TSL:5	c.829G>A	p.Val277Ile	missense splice_region	Exon 2 of 5	ENSP00000334665.7	O14926-2

Frequencies

GnomAD3 genomes

AF:

0.000751

AC:

114

AN:

151862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000666

AC:

AN:

136642

AF XY:

0.000683

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000170

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000375

Gnomad NFE exome

AF:

0.00148

Gnomad OTH exome

AF:

0.000250

GnomAD4 exome

AF:

0.00120

AC:

1651

AN:

1376250

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

722

AN XY:

678640

show subpopulations

African (AFR)

AF:

0.0000639

AC:

AN:

31312

American (AMR)

AF:

0.000143

AC:

AN:

34852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24862

East Asian (EAS)

AF:

0.00

AC:

AN:

35076

South Asian (SAS)

AF:

0.0000895

AC:

AN:

78202

European-Finnish (FIN)

AF:

0.000469

AC:

AN:

34130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.00145

AC:

1557

AN:

1074656

Other (OTH)

AF:

0.00111

AC:

AN:

57512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

147

220

294

367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000757

AC:

115

AN:

151982

Hom.:

Cov.:

AF XY:

0.000660

AC XY:

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41424

American (AMR)

AF:

0.000196

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00149

AC:

101

AN:

67906

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000255

Hom.:

Bravo

AF:

0.000722

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00189

AC:

ExAC

AF:

0.000404

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Retinitis pigmentosa 30 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.096

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.63

M_CAP

Benign

0.012

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.14

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.45

REVEL

Benign

0.033

Sift

Benign

0.23

Sift4G

Benign

0.55

Polyphen

0.0020

Vest4

0.073

MVP

0.18

MPC

0.065

ClinPred

0.014

GERP RS

-0.030

Varity_R

0.034

gMVP

0.15

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over