15-82759594-C-G

Variant names:

• chr15-82759594-C-G
• NM_001007122.4:c.2004G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007122.4(FSD2):​c.2004G>C​(p.Lys668Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FSD2 NM_001007122.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.250

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]

ACMG classification

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=0.20505929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSD2	NM_001007122.4	c.2004G>C	p.Lys668Asn	missense_variant	Exon 13 of 13	ENST00000334574.12	NP_001007123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSD2	ENST00000334574.12	c.2004G>C	p.Lys668Asn	missense_variant	Exon 13 of 13	1	NM_001007122.4	ENSP00000335651.8
FSD2	ENST00000541889.1	c.1869G>C	p.Lys623Asn	missense_variant	Exon 12 of 12	1		ENSP00000444078.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2004G>C (p.K668N) alteration is located in exon 13 (coding exon 12) of the FSD2 gene. This alteration results from a G to C substitution at nucleotide position 2004, causing the lysine (K) at amino acid position 668 to be replaced by an asparagine (N). 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	Uncertain	0.54
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	0.051
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.034	D;D
Polyphen		0.95	P;.
Vest4		0.10
MutPred		0.53		Gain of sheet (P = 0.0149);.;
MVP		0.57
MPC		0.070
ClinPred		0.95	D
GERP RS		1.2
Varity_R		0.36
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-83428346;