Variant 10-72062897-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 14/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Variant links:

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]

SPOCK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPOCK2	NM_001244950.2 linkuse as main transcript	c.1138G>A	p.Val380Met	missense_variant	11/11	ENST00000373109.7
SPOCK2	NM_014767.2 linkuse as main transcript	c.1138G>A	p.Val380Met	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPOCK2	ENST00000373109.7 linkuse as main transcript	c.1138G>A	p.Val380Met	missense_variant	11/11	1	NM_001244950.2	P1	Q92563-1
SPOCK2	ENST00000317376.8 linkuse as main transcript	c.1138G>A	p.Val380Met	missense_variant	12/12	1		P1	Q92563-1
SPOCK2	ENST00000463279.6 linkuse as main transcript	n.706G>A		non_coding_transcript_exon_variant	7/7	5
SPOCK2	ENST00000469121.5 linkuse as main transcript	n.774G>A		non_coding_transcript_exon_variant	7/7	3

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000972

AC:

AN:

226306

Hom.:

AF XY:

0.000123

AC XY:

AN XY:

122412

show subpopulations

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 SAS exome

AF:

0.0000703

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.:

Cov.:

AF XY:

0.0000752

AC XY:

AN XY:

718490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000927

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.0000420

Gnomad4 NFE exome

AF:

0.0000651

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

AF:

0.000105

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000418

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000149

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 17, 2022

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

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.085

T;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.032

FATHMM_MKL

Uncertain

0.83

M_CAP

Benign

0.024

MetaRNN

Benign

0.044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

N;N;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.63

REVEL

Benign

0.030

Sift4G

Benign

0.26

T;T;T

Polyphen

0.27

B;B;.

Vest4

0.066

MVP

0.18

MPC

0.28

ClinPred

0.044

GERP RS

4.4

Varity_R

0.070

gMVP

0.45

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over