rs201652340

Variant names:

• chr17-81528587-A-T
• rs201652340
• NM_012418.4:c.56A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_012418.4(FSCN2):​c.56A>T​(p.Asp19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,456,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D19H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: FSCN2 NM_012418.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.71
• Publications: 1 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15332487).
• BS2: High AC in GnomAdExome4 at 45 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.56A>T	p.Asp19Val	missense	Exon 1 of 5	NP_036550.1	O14926-1
	FSCN2	NM_001077182.3		c.56A>T	p.Asp19Val	missense	Exon 1 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.56A>T	p.Asp19Val	missense	Exon 1 of 5	ENSP00000388716.2	O14926-1
	FSCN2	ENST00000334850.7	TSL:5	c.56A>T	p.Asp19Val	missense	Exon 1 of 5	ENSP00000334665.7	O14926-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000836 AC: 2 AN: 239104 AF XY: 0.00000766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000938

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.0000309 AC: 45 AN: 1456870 Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 20 AN XY: 724322

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.0000226 AC: 1 AN: 44300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.00 AC: 0 AN: 85514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1110210

Other (OTH) AF: 0.00 AC: 0 AN: 60198

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000238 AC: 2

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.75
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.50	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.10
Sift	Benign	0.046	D
Sift4G	Benign	0.41	T
Polyphen		0.26	B
Vest4		0.36
MVP		0.49
MPC		0.14
ClinPred		0.069	T
GERP RS		4.0
PromoterAI		0.045	Neutral
Varity_R		0.092
gMVP		0.58
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs201652340; hg19: chr17-79495613;