Variant 17-81528579-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_012418.4(FSCN2):c.48C>T(p.Leu16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,608,430 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

FSCN2
NM_012418.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.85

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-81528579-C-T is Benign according to our data. Variant chr17-81528579-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 289847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81528579-C-T is described in Lovd as [Likely_benign]. Variant chr17-81528579-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.86 with no splicing effect.

BS2

High AC in GnomAd4 at 245 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSCN2	NM_012418.4 linkuse as main transcript	c.48C>T	p.Leu16=	synonymous_variant	1/5	ENST00000417245.7	NP_036550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSCN2	ENST00000417245.7 linkuse as main transcript	c.48C>T	p.Leu16=	synonymous_variant	1/5	1	NM_012418.4	ENSP00000388716	P1	O14926-1
FSCN2	ENST00000334850.7 linkuse as main transcript	c.48C>T	p.Leu16=	synonymous_variant	1/5	5		ENSP00000334665		O14926-2

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

244

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00238

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00197

AC:

468

AN:

238072

Hom.:

AF XY:

0.00215

AC XY:

279

AN XY:

129922

show subpopulations

Gnomad AFR exome

AF:

0.000138

Gnomad AMR exome

AF:

0.000917

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.0000571

Gnomad SAS exome

AF:

0.00271

Gnomad FIN exome

AF:

0.00531

Gnomad NFE exome

AF:

0.00219

Gnomad OTH exome

AF:

0.00170

GnomAD4 exome

AF:

0.00170

AC:

2478

AN:

1456074

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1234

AN XY:

723874

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.000905

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00244

Gnomad4 FIN exome

AF:

0.00558

Gnomad4 NFE exome

AF:

0.00166

Gnomad4 OTH exome

AF:

0.00125

GnomAD4 genome

AF:

0.00161

AC:

245

AN:

152356

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00240

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00105

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	FSCN2: BP4, BP7 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 15, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.051

DANN

Benign

0.85

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