Variant 4-1170566-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012445.4(SPON2):c.647C>T(p.Ser216Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,610,980 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SPON2
NM_012445.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

SPON2 (HGNC:11253): (spondin 2) Predicted to enable antigen binding activity; lipopolysaccharide binding activity; and metal ion binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within several processes, including defense response to other organism; opsonization; and positive regulation of cytokine production. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SPON2 links:

LOC124900647 (HGNC:):

LOC124900647 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPON2	NM_012445.4 link	c.647C>T	p.Ser216Phe	missense_variant	5/6	ENST00000290902.10	NP_036577.2	Q9BUD6
SPON2	NM_001128325.3 link	c.647C>T	p.Ser216Phe	missense_variant	6/7		NP_001121797.2	Q9BUD6
SPON2	NM_001199021.2 link	c.647C>T	p.Ser216Phe	missense_variant	7/8		NP_001185950.2	Q9BUD6
LOC124900647	XM_047416477.1 link	c.-2486-20534G>A		intron_variant			XP_047272433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPON2	ENST00000290902.10 link	c.647C>T	p.Ser216Phe	missense_variant	5/6	1	NM_012445.4	ENSP00000290902.5	Q9BUD6
SPON2	ENST00000431380.5 link	c.647C>T	p.Ser216Phe	missense_variant	6/7	5		ENSP00000394832.1	Q9BUD6
SPON2	ENST00000617421.4 link	c.647C>T	p.Ser216Phe	missense_variant	7/8	5		ENSP00000483599.1	Q9BUD6
SPON2	ENST00000509697.1 link	n.83C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000813

AC:

AN:

245978

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133346

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460874

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150106

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.647C>T (p.S216F) alteration is located in exon 7 (coding exon 4) of the SPON2 gene. This alteration results from a C to T substitution at nucleotide position 647, causing the serine (S) at amino acid position 216 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.97

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-0.43

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.9

D;D;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.0070

D;D;.

Sift4G

Uncertain

0.011

D;D;D

Vest4

0.48

MutPred

0.48

Loss of glycosylation at P221 (P = 0.0165);Loss of glycosylation at P221 (P = 0.0165);Loss of glycosylation at P221 (P = 0.0165);

MVP

0.68

MPC

0.89

ClinPred

0.96

GERP RS

5.2

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over