NM_012418.4:c.49G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012418.4(FSCN2):c.49G>A(p.Val17Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,608,570 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0034 ( 12 hom. )

Consequence

FSCN2
NM_012418.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 1.09

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014135033).

BP6

Variant 17-81528580-G-A is Benign according to our data. Variant chr17-81528580-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 100561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81528580-G-A is described in Lovd as [Benign]. Variant chr17-81528580-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 369 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN2	NM_012418.4 link	c.49G>A	p.Val17Ile	missense_variant	Exon 1 of 5	ENST00000417245.7	NP_036550.1	O14926-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSCN2	ENST00000417245.7 link	c.49G>A	p.Val17Ile	missense_variant	Exon 1 of 5	1	NM_012418.4	ENSP00000388716.2		O14926-1
FSCN2	ENST00000334850.7 link	c.49G>A	p.Val17Ile	missense_variant	Exon 1 of 5	5		ENSP00000334665.7		O14926-2

Frequencies

GnomAD3 genomes

AF:

0.00244

AC:

371

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00376

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00229

AC:

546

AN:

238348

Hom.:

AF XY:

0.00235

AC XY:

306

AN XY:

130088

show subpopulations

Gnomad AFR exome

AF:

0.000481

Gnomad AMR exome

AF:

0.000887

Gnomad ASJ exome

AF:

0.000204

Gnomad EAS exome

AF:

0.000171

Gnomad SAS exome

AF:

0.000743

Gnomad FIN exome

AF:

0.00458

Gnomad NFE exome

AF:

0.00350

Gnomad OTH exome

AF:

0.00238

GnomAD4 exome

AF:

0.00345

AC:

5021

AN:

1456202

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

2413

AN XY:

723966

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.00113

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.000749

Gnomad4 FIN exome

AF:

0.00492

Gnomad4 NFE exome

AF:

0.00403

Gnomad4 OTH exome

AF:

0.00254

GnomAD4 genome

AF:

0.00242

AC:

369

AN:

152368

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00375

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00332

Hom.:

Bravo

AF:

0.00207

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000958

AC:

ESP6500EA

AF:

0.00262

AC:

ExAC

AF:

0.00215

AC:

260

ClinVar

Significance: Likely benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

NEI Ophthalmic Genomics Laboratory, National Institutes of Health

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FSCN2: BP4, BS1 -

Retinitis pigmentosa 30

Benign:2

Feb 28, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 09, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.028

DANN

Benign

0.86

DEOGEN2

Benign

0.074

T;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.1

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.48

N;N

REVEL

Benign

0.088

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;.

Vest4

0.064

MVP

0.061

MPC

0.060

ClinPred

0.0059

GERP RS

-5.3

Varity_R

0.019

gMVP

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over