NM_001007122.4:c.2095A>G

Variant names:

• chr15-82759503-T-C
• rs760080782
• NM_001007122.4:c.2095A>G

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.2095A>G​(p.Lys699Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000645 in 1,612,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: FSD2 NM_001007122.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46
• 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=0.18031737).

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.2095A>G	p.Lys699Glu	missense	Exon 13 of 13	NP_001007123.1	A1L4K1-1
	FSD2	NM_001281805.2		c.1960A>G	p.Lys654Glu	missense	Exon 13 of 13	NP_001268734.1	A1L4K1-2
	FSD2	NM_001281806.2		c.1960A>G	p.Lys654Glu	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.2095A>G	p.Lys699Glu	missense	Exon 13 of 13	ENSP00000335651.8	A1L4K1-1
	FSD2	ENST00000541889.1	TSL:1	c.1960A>G	p.Lys654Glu	missense	Exon 12 of 12	ENSP00000444078.1	A1L4K1-2
	FSD2	ENST00000961201.1		c.2095A>G	p.Lys699Glu	missense	Exon 14 of 14	ENSP00000631260.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000285 AC: 7 AN: 245978 AF XY: 0.0000225

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000586

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000449

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000685 AC: 100 AN: 1460242 Hom.: 0 Cov.: 31 AF XY: 0.0000675 AC XY: 49 AN XY: 726264

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.0000674 AC: 3 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 85918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000756 AC: 84 AN: 1111122

Other (OTH) AF: 0.000215 AC: 13 AN: 60336

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74364

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000806 Hom.: 0

Bravo AF: 0.0000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

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	0.20
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.77	N
PhyloP100		4.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.19
Sift	Uncertain	0.018	D
Sift4G	Benign	0.12	T
Polyphen		0.85	P
Vest4		0.34
MVP		0.36
MPC		0.22
ClinPred		0.54	D
GERP RS		4.7
Varity_R		0.44
gMVP		0.47
Mutation Taster		=86/14	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: rs760080782; hg19: chr15-83428255;