15-82765182-C-A

Variant summary

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

The NM_001007122.4(FSD2):​c.1804G>T​(p.Asp602Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000748 in 1,604,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. D602H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

FSD2
NM_001007122.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28
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=0.22502917).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FSD2NM_001007122.4 linkc.1804G>T p.Asp602Tyr missense_variant Exon 11 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.1804G>T p.Asp602Tyr missense_variant Exon 11 of 13 1 NM_001007122.4 ENSP00000335651.8 A1L4K1-1
FSD2ENST00000541889.1 linkc.1669G>T p.Asp557Tyr missense_variant Exon 10 of 12 1 ENSP00000444078.1 A1L4K1-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152040
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.00000412
AC:
1
AN:
242670
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132022
show subpopulations
Gnomad AFR exome
AF:
0.0000656
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000551
AC:
8
AN:
1452192
Hom.:
0
Cov.:
30
AF XY:
0.00000554
AC XY:
4
AN XY:
721668
show subpopulations
Gnomad4 AFR exome
AF:
0.000212
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152040
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.0000725
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.0000193
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1804G>T (p.D602Y) alteration is located in exon 11 (coding exon 10) of the FSD2 gene. This alteration results from a G to T substitution at nucleotide position 1804, causing the aspartic acid (D) at amino acid position 602 to be replaced by a tyrosine (Y). 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
0.11
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
7.2
DANN
Benign
0.97
DEOGEN2
Benign
0.040
T;.
Eigen
Benign
-0.79
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.58
T;T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.9
N;N
REVEL
Benign
0.21
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.99
D;.
Vest4
0.26
MVP
0.20
MPC
0.061
ClinPred
0.94
D
GERP RS
-8.8
Varity_R
0.066
gMVP
0.51

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs979074782; hg19: chr15-83433934; API