rs200859576

Variant names:

• chr10-72062897-C-G
• rs200859576
• NM_001244950.2:c.1138G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-72062897-C-G
• chr10-72062897-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001244950.2(SPOCK2):​c.1138G>C​(p.Val380Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,446,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V380M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SPOCK2 NM_001244950.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

Genes affected

SPOCK2 (HGNC:13564): (SPARC (osteonectin), cwcv and kazal like domains proteoglycan 2) This gene encodes a protein which binds with glycosaminoglycans to form part of the extracellular matrix. The protein contains thyroglobulin type-1, follistatin-like, and calcium-binding domains, and has glycosaminoglycan attachment sites in the acidic C-terminal region. Three alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

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=0.084569484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK2	NM_001244950.2	c.1138G>C	p.Val380Leu	missense_variant	Exon 11 of 11	ENST00000373109.7	NP_001231879.1
SPOCK2	NM_014767.2	c.1138G>C	p.Val380Leu	missense_variant	Exon 12 of 12		NP_055582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK2	ENST00000373109.7	c.1138G>C	p.Val380Leu	missense_variant	Exon 11 of 11	1	NM_001244950.2	ENSP00000362201.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1446134 Hom.: 0 Cov.: 74 AF XY: 0.00 AC XY: 0 AN XY: 718492

African (AFR) AF: 0.00 AC: 0 AN: 33238

American (AMR) AF: 0.00 AC: 0 AN: 43158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25782

East Asian (EAS) AF: 0.00 AC: 0 AN: 39366

South Asian (SAS) AF: 0.00 AC: 0 AN: 84566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47666

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

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1106658

Other (OTH) AF: 0.0000334 AC: 2 AN: 59940

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.075	T;T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.62	.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L;.
PhyloP100		1.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.35	.;N;.
REVEL	Benign	0.031
Sift	Benign	0.38	.;T;.
Sift4G	Benign	0.77	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.057
MutPred		0.30		Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);.;
MVP		0.14
MPC		0.28
ClinPred		0.45	T
GERP RS		4.4
Varity_R		0.086
gMVP		0.46
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200859576; hg19: chr10-73822655;