17-81528602-TG-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PVS1_StrongBS2

The NM_012418.4(FSCN2):c.72delG(p.Thr25GlnfsTer120) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000354 in 1,609,000 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L24L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00035 ( 3 hom. )

Consequence

FSCN2
NM_012418.4 frameshift

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2U:2B:2

Conservation

PhyloP100: 0.644

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.

BS2

High AC in GnomAd4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN2	NM_012418.4 link	c.72delG	p.Thr25GlnfsTer120	frameshift_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.72delG	p.Thr25GlnfsTer120	frameshift_variant	Exon 1 of 5	1	NM_012418.4	ENSP00000388716.2		O14926-1
FSCN2	ENST00000334850.7 link	c.72delG	p.Thr25GlnfsTer120	frameshift_variant	Exon 1 of 5	5		ENSP00000334665.7		O14926-2

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0111

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000931

AC:

222

AN:

238454

AF XY:

0.000930

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000349

AC:

509

AN:

1456632

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

257

AN XY:

724264

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33408

Gnomad4 AMR exome

AF:

0.0000226

AC:

AN:

44240

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26026

Gnomad4 EAS exome

AF:

0.0112

AC:

444

AN:

39506

Gnomad4 SAS exome

AF:

0.000339

AC:

AN:

85472

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

51864

Gnomad4 NFE exome

AF:

0.00000450

AC:

AN:

1110156

Gnomad4 Remaining exome

AF:

0.000498

AC:

AN:

60192

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000394

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.0114

AC:

0.0113593

AN:

0.0113593

Gnomad4 SAS

AF:

0.000207

AC:

0.000206954

AN:

0.000206954

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.0000434

Hom.:

Bravo

AF:

0.000438

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:2Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Department of Ophthalmology and Visual Sciences Kyoto University

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Dec 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 30

Pathogenic:1

Sep 01, 2008

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Macular degeneration

Pathogenic:1

Sep 01, 2008

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Leber congenital amaurosis

Uncertain:1

Sep 18, 2014

Molecular Diagnostics Laboratory, Seoul National University Hospital

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Retinal dystrophy

Uncertain:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=174/26

disease causing (ClinVar)

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