rs7689089

Variant names:

• chr4-1170520-C-A
• rs7689089
• NM_012445.4:c.693G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-1170520-C-A
• chr4-1170520-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012445.4(SPON2):​c.693G>T​(p.Lys231Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K231K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SPON2 NM_012445.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

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]

LOC124900647 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012445.4. 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
	SPON2	NM_012445.4	MANE Select	c.693G>T	p.Lys231Asn	missense	Exon 5 of 6	NP_036577.2	Q9BUD6
	SPON2	NM_001128325.3		c.693G>T	p.Lys231Asn	missense	Exon 6 of 7	NP_001121797.2	Q9BUD6
	SPON2	NM_001199021.2		c.693G>T	p.Lys231Asn	missense	Exon 7 of 8	NP_001185950.2	Q9BUD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPON2	ENST00000290902.10	TSL:1 MANE Select	c.693G>T	p.Lys231Asn	missense	Exon 5 of 6	ENSP00000290902.5	Q9BUD6
	SPON2	ENST00000960395.1		c.1017G>T	p.Lys339Asn	missense	Exon 5 of 6	ENSP00000630454.1
	SPON2	ENST00000431380.5	TSL:5	c.693G>T	p.Lys231Asn	missense	Exon 6 of 7	ENSP00000394832.1	Q9BUD6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 7

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Benign	0.13
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.0	T
PhyloP100		1.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.12
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Vest4		0.55
MutPred		0.65		Loss of methylation at K231 (P = 0.004)
MVP		0.61
MPC		0.64
ClinPred		0.98	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.71
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7689089; hg19: chr4-1164308;