rs143796236

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012418.4(FSCN2):c.412C>T(p.His138Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 1,590,356 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 4 hom., cov: 34)

Exomes 𝑓: 0.0078 ( 56 hom. )

Consequence

FSCN2
NM_012418.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 7.29

Publications

16 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), G2P, Ambry Genetics

FSCN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010590553).

BP6

Variant 17-81528943-C-T is Benign according to our data. Variant chr17-81528943-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 167106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 925 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN2	NM_012418.4 link	c.412C>T	p.His138Tyr	missense_variant	Exon 1 of 5	ENST00000417245.7	NP_036550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSCN2	ENST00000417245.7 link	c.412C>T	p.His138Tyr	missense_variant	Exon 1 of 5	1	NM_012418.4	ENSP00000388716.2
FSCN2	ENST00000334850.7 link	c.412C>T	p.His138Tyr	missense_variant	Exon 1 of 5	5		ENSP00000334665.7

Frequencies

GnomAD3 genomes

AF:

0.00606

AC:

923

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00894

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00907

Gnomad OTH

AF:

0.00812

GnomAD2 exomes

AF:

0.00714

AC:

1485

AN:

208014

AF XY:

0.00721

show subpopulations

Gnomad AFR exome

AF:

0.000964

Gnomad AMR exome

AF:

0.00268

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00812

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.00776

AC:

11157

AN:

1437990

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

5577

AN XY:

714244

show subpopulations

African (AFR)

AF:

0.00124

AC:

AN:

33074

American (AMR)

AF:

0.00277

AC:

119

AN:

42998

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

370

AN:

25704

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38724

South Asian (SAS)

AF:

0.00528

AC:

440

AN:

83348

European-Finnish (FIN)

AF:

0.00901

AC:

401

AN:

44490

Middle Eastern (MID)

AF:

0.0115

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00840

AC:

9279

AN:

1104408

Other (OTH)

AF:

0.00740

AC:

441

AN:

59606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

754

1508

2262

3016

3770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.00607

AC:

925

AN:

152366

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

453

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41590

American (AMR)

AF:

0.00301

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00497

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00894

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00909

AC:

618

AN:

68024

Other (OTH)

AF:

0.00803

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00829

Hom.:

Bravo

AF:

0.00527

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.000239

AC:

ESP6500EA

AF:

0.00851

AC:

ExAC

AF:

0.00690

AC:

819

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 10, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FSCN2: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 23, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

D;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

7.3

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.3

D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;.

Vest4

0.85

MVP

0.66

MPC

0.45

ClinPred

0.0095

GERP RS

4.8

PromoterAI

0.0027

Neutral

(source)

Varity_R

0.79

gMVP

0.86

Mutation Taster

=73/27

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over