rs186367879

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012418.4(FSCN2):c.967G>A(p.Ala323Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 1,530,642 control chromosomes in the GnomAD database, including 908 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 66 hom., cov: 31)

Exomes 𝑓: 0.033 ( 842 hom. )

Consequence

FSCN2
NM_012418.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.815

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032982528).

BP6

Variant 17-81535192-G-A is Benign according to our data. Variant chr17-81535192-G-A is described in ClinVar as [Benign]. Clinvar id is 402883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81535192-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0256 (3891/151798) while in subpopulation NFE AF= 0.0375 (2545/67880). AF 95% confidence interval is 0.0363. There are 66 homozygotes in gnomad4. There are 1883 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3891 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN2	NM_012418.4 link	c.967G>A	p.Ala323Thr	missense_variant	Exon 2 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.967G>A	p.Ala323Thr	missense_variant	Exon 2 of 5	1	NM_012418.4	ENSP00000388716.2		O14926-1
FSCN2	ENST00000334850.7 link	c.967G>A	p.Ala323Thr	missense_variant	Exon 2 of 5	5		ENSP00000334665.7		O14926-2

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3892

AN:

151680

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00669

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0276

Gnomad ASJ

AF:

0.0613

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00623

Gnomad FIN

AF:

0.0281

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0375

Gnomad OTH

AF:

0.0360

GnomAD3 exomes

AF:

0.0267

AC:

3616

AN:

135440

Hom.:

AF XY:

0.0264

AC XY:

1926

AN XY:

72836

show subpopulations

Gnomad AFR exome

AF:

0.00559

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0569

Gnomad EAS exome

AF:

0.0000998

Gnomad SAS exome

AF:

0.00688

Gnomad FIN exome

AF:

0.0252

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0316

GnomAD4 exome

AF:

0.0332

AC:

45783

AN:

1378844

Hom.:

842

Cov.:

AF XY:

0.0328

AC XY:

22346

AN XY:

680324

show subpopulations

Gnomad4 AFR exome

AF:

0.00669

Gnomad4 AMR exome

AF:

0.0224

Gnomad4 ASJ exome

AF:

0.0580

Gnomad4 EAS exome

AF:

0.0000566

Gnomad4 SAS exome

AF:

0.00689

Gnomad4 FIN exome

AF:

0.0264

Gnomad4 NFE exome

AF:

0.0369

Gnomad4 OTH exome

AF:

0.0324

GnomAD4 genome

AF:

0.0256

AC:

3891

AN:

151798

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1883

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.00667

Gnomad4 AMR

AF:

0.0275

Gnomad4 ASJ

AF:

0.0613

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.00624

Gnomad4 FIN

AF:

0.0281

Gnomad4 NFE

AF:

0.0375

Gnomad4 OTH

AF:

0.0356

Alfa

AF:

0.0374

Hom.:

Bravo

AF:

0.0248

TwinsUK

AF:

0.0372

AC:

138

ALSPAC

AF:

0.0371

AC:

143

ESP6500AA

AF:

0.00506

AC:

ESP6500EA

AF:

0.0361

AC:

115

ExAC

AF:

0.0151

AC:

411

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Benign

0.068

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.093

Sift

Uncertain

0.014

D;D

Sift4G

Benign

0.16

T;T

Polyphen

0.65

P;.

Vest4

0.34

MPC

0.20

ClinPred

0.0091

GERP RS

3.9

Varity_R

0.18

gMVP

0.39

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