15-82765931-C-G

Variant names:

• chr15-82765931-C-G
• rs759649017
• NM_001007122.4:c.1654G>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.1654G>C​(p.Val552Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. V552M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FSD2 NM_001007122.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• 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=0.10334048).

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.1654G>C	p.Val552Leu	missense	Exon 10 of 13	NP_001007123.1	A1L4K1-1
	FSD2	NM_001281805.2		c.1519G>C	p.Val507Leu	missense	Exon 10 of 13	NP_001268734.1	A1L4K1-2
	FSD2	NM_001281806.2		c.1519G>C	p.Val507Leu	missense	Exon 9 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.1654G>C	p.Val552Leu	missense	Exon 10 of 13	ENSP00000335651.8	A1L4K1-1
	FSD2	ENST00000541889.1	TSL:1	c.1519G>C	p.Val507Leu	missense	Exon 9 of 12	ENSP00000444078.1	A1L4K1-2
	FSD2	ENST00000961201.1		c.1654G>C	p.Val552Leu	missense	Exon 11 of 14	ENSP00000631260.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457974 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724880

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5252

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110864

Other (OTH) AF: 0.00 AC: 0 AN: 60224

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.9
DANN	Benign	0.87
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.034
Sift	Benign	0.033	D
Sift4G	Benign	0.14	T
Polyphen		0.017	B
Vest4		0.13
MutPred		0.22		Gain of glycosylation at P550 (P = 0.0929)
MVP		0.17
MPC		0.050
ClinPred		0.18	T
GERP RS		3.7
Varity_R		0.072
gMVP		0.19

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

dbSNP: rs759649017; hg19: chr15-83434683;