15-82765931-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001007122.4(FSD2):​c.1654G>A​(p.Val552Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,610,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

FSD2
NM_001007122.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92
Variant links:
Genes affected
FSD2 (HGNC:18024): (fibronectin type III and SPRY domain containing 2) This gene encodes a protein that belongs to the FN3/SPRY family of proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10609454).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FSD2NM_001007122.4 linkc.1654G>A p.Val552Met missense_variant Exon 10 of 13 ENST00000334574.12 NP_001007123.1 A1L4K1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FSD2ENST00000334574.12 linkc.1654G>A p.Val552Met missense_variant Exon 10 of 13 1 NM_001007122.4 ENSP00000335651.8 A1L4K1-1
FSD2ENST00000541889.1 linkc.1519G>A p.Val507Met missense_variant Exon 9 of 12 1 ENSP00000444078.1 A1L4K1-2

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152200
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000869
AC:
21
AN:
241752
Hom.:
0
AF XY:
0.000107
AC XY:
14
AN XY:
131232
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000887
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000163
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000169
AC:
246
AN:
1457974
Hom.:
0
Cov.:
31
AF XY:
0.000182
AC XY:
132
AN XY:
724880
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000677
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000217
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152200
Hom.:
0
Cov.:
31
AF XY:
0.000148
AC XY:
11
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000181
Hom.:
0
Bravo
AF:
0.000151
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000745
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 15, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1654G>A (p.V552M) alteration is located in exon 10 (coding exon 9) of the FSD2 gene. This alteration results from a G to A substitution at nucleotide position 1654, causing the valine (V) at amino acid position 552 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
10
DANN
Benign
0.97
DEOGEN2
Benign
0.024
T;.
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.37
N
LIST_S2
Benign
0.46
T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.090
N;N
REVEL
Benign
0.069
Sift
Uncertain
0.022
D;D
Sift4G
Uncertain
0.051
T;T
Polyphen
0.75
P;.
Vest4
0.22
MVP
0.24
MPC
0.070
ClinPred
0.082
T
GERP RS
3.7
Varity_R
0.043
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs759649017; hg19: chr15-83434683; API