17-81528579-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.85

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]

ACMG classification

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 GnomAd at 244 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSCN2	ENST00000417245.7	c.48C>T	p.Leu16=	synonymous_variant	1/5	1	NM_012418.4	P1
FSCN2	ENST00000334850.7	c.48C>T	p.Leu16=	synonymous_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 244 AN: 152238 Hom.: 0 Cov.: 34

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.: 2 AF XY: 0.00215 AC XY: 279 AN XY: 129922

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.: 3 Cov.: 32 AF XY: 0.00170 AC XY: 1234 AN XY: 723874

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.: 0 Cov.: 34 AF XY: 0.00177 AC XY: 132 AN XY: 74506

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.: 0

Bravo AF: 0.00105

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	FSCN2: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -

not specified Benign:2

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

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

Other links and lift over

dbSNP: rs199668780; hg19: chr17-79495605; COSMIC: COSV58368402; COSMIC: COSV58368402;