15-82765223-C-T

Variant names:

• chr15-82765223-C-T
• rs757036146
• NM_001007122.4:c.1763G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001007122.4(FSD2):​c.1763G>A​(p.Arg588Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,610,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: FSD2 NM_001007122.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43
• Publications: 2 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31041098).

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.1763G>A	p.Arg588Gln	missense	Exon 11 of 13	NP_001007123.1	A1L4K1-1
	FSD2	NM_001281805.2		c.1628G>A	p.Arg543Gln	missense	Exon 11 of 13	NP_001268734.1	A1L4K1-2
	FSD2	NM_001281806.2		c.1628G>A	p.Arg543Gln	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.1763G>A	p.Arg588Gln	missense	Exon 11 of 13	ENSP00000335651.8	A1L4K1-1
	FSD2	ENST00000541889.1	TSL:1	c.1628G>A	p.Arg543Gln	missense	Exon 10 of 12	ENSP00000444078.1	A1L4K1-2
	FSD2	ENST00000961201.1		c.1763G>A	p.Arg588Gln	missense	Exon 12 of 14	ENSP00000631260.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152034 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000243 AC: 6 AN: 246670 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1458608 Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21 AN XY: 725438

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.000158 AC: 7 AN: 44172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 85810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1110310

Other (OTH) AF: 0.0000830 AC: 5 AN: 60250

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152152 Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6 AN XY: 74390

African (AFR) AF: 0.0000241 AC: 1 AN: 41504

American (AMR) AF: 0.000458 AC: 7 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000121

ExAC AF: 0.00000827 AC: 1

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.25
Sift	Benign	0.29	T
Sift4G	Benign	0.41	T
Polyphen		1.0	D
Vest4		0.38
MutPred		0.53		Gain of sheet (P = 0.0827)
MVP		0.31
MPC		0.30
ClinPred		0.85	D
GERP RS		5.6
Varity_R		0.13
gMVP		0.57
Mutation Taster		=81/19	polymorphism

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: rs757036146; hg19: chr15-83433975; COSMIC: COSV58009471;