NM_001244950.2:c.1138G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001244950.2(SPOCK2):​c.1138G>A​(p.Val380Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000826 in 1,598,252 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000080 (1 hom.)
• Consequence: SPOCK2 NM_001244950.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044466943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK2	NM_001244950.2	c.1138G>A	p.Val380Met	missense_variant	Exon 11 of 11	ENST00000373109.7	NP_001231879.1
SPOCK2	NM_014767.2	c.1138G>A	p.Val380Met	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>A	p.Val380Met	missense_variant	Exon 11 of 11	1	NM_001244950.2	ENSP00000362201.2

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152002 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.0000972 AC: 22 AN: 226306 AF XY: 0.000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000616

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000576

Gnomad NFE exome AF: 0.000148

Gnomad OTH exome AF: 0.000351

GnomAD4 exome AF: 0.0000802 AC: 116 AN: 1446132 Hom.: 1 Cov.: 74 AF XY: 0.0000752 AC XY: 54 AN XY: 718490

African (AFR) AF: 0.0000301 AC: 1 AN: 33238

American (AMR) AF: 0.0000927 AC: 4 AN: 43158

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

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39366

South Asian (SAS) AF: 0.000106 AC: 9 AN: 84566

European-Finnish (FIN) AF: 0.0000420 AC: 2 AN: 47666

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5760

European-Non Finnish (NFE) AF: 0.0000651 AC: 72 AN: 1106656

Other (OTH) AF: 0.0000667 AC: 4 AN: 59940

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152120 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41514

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4786

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67966

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000149 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1138G>A (p.V380M) alteration is located in exon 12 (coding exon 11) of the SPOCK2 gene. This alteration results from a G to A substitution at nucleotide position 1138, causing the valine (V) at amino acid position 380 to be replaced by a methionine (M). 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	0.091
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.032
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.70	.;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N;N;.
PhyloP100		1.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.15	.;N;.
REVEL	Benign	0.030
Sift	Benign	0.15	.;T;.
Sift4G	Benign	0.26	T;T;T
Polyphen		0.27	B;B;.
Vest4		0.066
MVP		0.18
MPC		0.28
ClinPred		0.044	T
GERP RS		4.4
Varity_R		0.070
gMVP		0.45
Mutation Taster		=93/7	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: rs200859576; hg19: chr10-73822655; COSMIC: COSV100436360; COSMIC: COSV100436360;