chr15-82765286-C-A

Variant names:

• chr15-82765286-C-A
• rs765293776
• NM_001007122.4:c.1700G>T

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.1700G>T​(p.Arg567Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R567S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FSD2 NM_001007122.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• 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=0.0865967).

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.1700G>T	p.Arg567Leu	missense	Exon 11 of 13	NP_001007123.1	A1L4K1-1
	FSD2	NM_001281805.2		c.1565G>T	p.Arg522Leu	missense	Exon 11 of 13	NP_001268734.1	A1L4K1-2
	FSD2	NM_001281806.2		c.1565G>T	p.Arg522Leu	missense	Exon 10 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.1700G>T	p.Arg567Leu	missense	Exon 11 of 13	ENSP00000335651.8	A1L4K1-1
	FSD2	ENST00000541889.1	TSL:1	c.1565G>T	p.Arg522Leu	missense	Exon 10 of 12	ENSP00000444078.1	A1L4K1-2
	FSD2	ENST00000961201.1		c.1700G>T	p.Arg567Leu	missense	Exon 12 of 14	ENSP00000631260.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.4
DANN	Benign	0.65
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.045	N
PhyloP100		-0.35
PrimateAI	Benign	0.19	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.080
Sift	Benign	0.74	T
Sift4G	Benign	0.17	T
Polyphen		0.086	B
Vest4		0.34
MutPred		0.70		Gain of methylation at K570 (P = 0.0378)
MVP		0.092
MPC		0.063
ClinPred		0.093	T
GERP RS		-3.5
Varity_R		0.062
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs765293776; hg19: chr15-83434038;