dbSNP rs1201286338: SPON2:p.Val305Phe (chr4-1167555-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012445.4(SPON2):c.913G>T(p.Val305Phe) 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. 11/19 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. V305I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SPON2
NM_012445.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0790

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:

ENSG00000273179 (HGNC:58121):

ENSG00000273179 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2997892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPON2	NM_012445.4 link	c.913G>T	p.Val305Phe	missense_variant	Exon 6 of 6	ENST00000290902.10	NP_036577.2	Q9BUD6
SPON2	NM_001128325.3 link	c.913G>T	p.Val305Phe	missense_variant	Exon 7 of 7		NP_001121797.2	Q9BUD6
SPON2	NM_001199021.2 link	c.913G>T	p.Val305Phe	missense_variant	Exon 8 of 8		NP_001185950.2	Q9BUD6
LOC124900647	XM_047416477.1 link	c.-2486-23545C>A		intron_variant	Intron 1 of 2		XP_047272433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPON2	ENST00000290902.10 link	c.913G>T	p.Val305Phe	missense_variant	Exon 6 of 6	1	NM_012445.4	ENSP00000290902.5	Q9BUD6
SPON2	ENST00000431380.5 link	c.913G>T	p.Val305Phe	missense_variant	Exon 7 of 7	5		ENSP00000394832.1	Q9BUD6
SPON2	ENST00000617421.4 link	c.913G>T	p.Val305Phe	missense_variant	Exon 8 of 8	5		ENSP00000483599.1	Q9BUD6
ENSG00000273179	ENST00000609548.1 link	n.-223C>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250756

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.045

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.73

M_CAP

Benign

0.060

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.0

D;D;.

REVEL

Benign

0.18

Sift

Uncertain

0.0030

D;D;.

Sift4G

Uncertain

0.0050

D;D;D

Vest4

0.47

MutPred

0.42

Gain of glycosylation at Y304 (P = 0.0351);Gain of glycosylation at Y304 (P = 0.0351);Gain of glycosylation at Y304 (P = 0.0351);

MVP

0.10

MPC

0.67

ClinPred

0.97

GERP RS

1.1

gMVP

0.80

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over