chr17-81528943-C-T

Position:

• chr17-81528943-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_012418.4(FSCN2):​c.412C>T​(p.His138Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 1,590,356 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (4 hom., cov: 34)
  • Exomes 𝑓: 0.0078 (56 hom.)
• Consequence: FSCN2 NM_012418.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 7.29

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010590553).
• BP6: Variant 17-81528943-C-T is Benign according to our data. Variant chr17-81528943-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 167106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81528943-C-T is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 925 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSCN2	NM_012418.4	c.412C>T	p.His138Tyr	missense_variant	1/5	ENST00000417245.7	NP_036550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSCN2	ENST00000417245.7	c.412C>T	p.His138Tyr	missense_variant	1/5	1	NM_012418.4	ENSP00000388716	P1
FSCN2	ENST00000334850.7	c.412C>T	p.His138Tyr	missense_variant	1/5	5		ENSP00000334665

Frequencies

GnomAD3 genomes AF: 0.00606 AC: 923 AN: 152248 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00894

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00907

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00714 AC: 1485 AN: 208014 Hom.: 10 AF XY: 0.00721 AC XY: 831 AN XY: 115226

Gnomad AFR exome AF: 0.000964

Gnomad AMR exome AF: 0.00268

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00525

Gnomad FIN exome AF: 0.00812

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00776 AC: 11157 AN: 1437990 Hom.: 56 Cov.: 33 AF XY: 0.00781 AC XY: 5577 AN XY: 714244

Gnomad4 AFR exome AF: 0.00124

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.0144

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.00528

Gnomad4 FIN exome AF: 0.00901

Gnomad4 NFE exome AF: 0.00840

Gnomad4 OTH exome AF: 0.00740

GnomAD4 genome AF: 0.00607 AC: 925 AN: 152366 Hom.: 4 Cov.: 34 AF XY: 0.00608 AC XY: 453 AN XY: 74510

Gnomad4 AFR AF: 0.00168

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.00894

Gnomad4 NFE AF: 0.00909

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00921 Hom.: 7

Bravo AF: 0.00527

TwinsUK AF: 0.00566 AC: 21

ALSPAC AF: 0.00960 AC: 37

ESP6500AA AF: 0.000239 AC: 1

ESP6500EA AF: 0.00851 AC: 71

ExAC AF: 0.00690 AC: 819

Asia WGS AF: 0.00751 AC: 29 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 10, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	FSCN2: BS2 -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 23, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.85
MVP		0.66
MPC		0.45
ClinPred		0.0095	T
GERP RS		4.8
Varity_R		0.79
gMVP		0.86

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: rs143796236; hg19: chr17-79495969;