chr15-82759594-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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]

SNHG21 (HGNC:50284): (small nucleolar RNA host gene 21)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20505929).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007122.4. 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
	FSD2	NM_001007122.4	MANE Select	c.2004G>C	p.Lys668Asn	missense	Exon 13 of 13	NP_001007123.1	A1L4K1-1
	FSD2	NM_001281805.2		c.1869G>C	p.Lys623Asn	missense	Exon 13 of 13	NP_001268734.1	A1L4K1-2
	FSD2	NM_001281806.2		c.1869G>C	p.Lys623Asn	missense	Exon 12 of 12	NP_001268735.1	A1L4K1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSD2	ENST00000334574.12	TSL:1 MANE Select	c.2004G>C	p.Lys668Asn	missense	Exon 13 of 13	ENSP00000335651.8	A1L4K1-1
	FSD2	ENST00000541889.1	TSL:1	c.1869G>C	p.Lys623Asn	missense	Exon 12 of 12	ENSP00000444078.1	A1L4K1-2
	FSD2	ENST00000961201.1		c.2004G>C	p.Lys668Asn	missense	Exon 14 of 14	ENSP00000631260.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.25
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.034	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

Other links and lift over

hg19: chr15-83428346;