chr17-81535192-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa 30
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

FSCN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 402883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 3891 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012418.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCN2	NM_012418.4	MANE Select	c.967G>A	p.Ala323Thr	missense	Exon 2 of 5	NP_036550.1	O14926-1
	FSCN2	NM_001077182.3		c.967G>A	p.Ala323Thr	missense	Exon 2 of 5	NP_001070650.1	O14926-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCN2	ENST00000417245.7	TSL:1 MANE Select	c.967G>A	p.Ala323Thr	missense	Exon 2 of 5	ENSP00000388716.2	O14926-1
	FSCN2	ENST00000334850.7	TSL:5	c.967G>A	p.Ala323Thr	missense	Exon 2 of 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

GnomAD2 exomes

AF:

0.0267

AC:

3616

AN:

135440

AF XY:

0.0264

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 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

African (AFR)

AF:

0.00669

AC:

210

AN:

31394

American (AMR)

AF:

0.0224

AC:

789

AN:

35148

Ashkenazi Jewish (ASJ)

AF:

0.0580

AC:

1449

AN:

24996

East Asian (EAS)

AF:

0.0000566

AC:

AN:

35328

South Asian (SAS)

AF:

0.00689

AC:

542

AN:

78636

European-Finnish (FIN)

AF:

0.0264

AC:

900

AN:

34042

Middle Eastern (MID)

AF:

0.0545

AC:

309

AN:

5668

European-Non Finnish (NFE)

AF:

0.0369

AC:

39716

AN:

1075972

Other (OTH)

AF:

0.0324

AC:

1866

AN:

57660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

1957

3914

5872

7829

9786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1482

2964

4446

5928

7410

<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:

0.0256

AC:

3891

AN:

151798

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1883

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.00667

AC:

276

AN:

41362

American (AMR)

AF:

0.0275

AC:

419

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0613

AC:

213

AN:

3472

East Asian (EAS)

AF:

0.000389

AC:

AN:

5138

South Asian (SAS)

AF:

0.00624

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0281

AC:

297

AN:

10574

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0375

AC:

2545

AN:

67880

Other (OTH)

AF:

0.0356

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

193

387

580

774

967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0351

Hom.:

269

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Benign

0.068

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

0.81

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.3

REVEL

Benign

0.093

Sift

Uncertain

0.014

Sift4G

Benign

0.16

Polyphen

0.65

Vest4

0.34

MPC

0.20

ClinPred

0.0091

GERP RS

3.9

Varity_R

0.18

gMVP

0.39

Mutation Taster

=79/21

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over