10-72063097-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001244950.2(SPOCK2):c.1057G>A(p.Gly353Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,555,236 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 32 hom. )

Consequence

SPOCK2
NM_001244950.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.81

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058939457).

BP6

Variant 10-72063097-C-T is Benign according to our data. Variant chr10-72063097-C-T is described in ClinVar as [Benign]. Clinvar id is 773516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00436 (6115/1402904) while in subpopulation EAS AF= 0.0229 (821/35924). AF 95% confidence interval is 0.0216. There are 32 homozygotes in gnomad4_exome. There are 3070 alleles in male gnomad4_exome subpopulation. Median coverage is 75. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK2	NM_001244950.2 link	c.1057G>A	p.Gly353Ser	missense_variant	Exon 10 of 11	ENST00000373109.7	NP_001231879.1	Q92563-1
SPOCK2	NM_014767.2 link	c.1057G>A	p.Gly353Ser	missense_variant	Exon 11 of 12		NP_055582.1	Q92563-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK2	ENST00000373109.7 link	c.1057G>A	p.Gly353Ser	missense_variant	Exon 10 of 11	1	NM_001244950.2	ENSP00000362201.2		Q92563-1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

529

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0164

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00356

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00412

AC:

666

AN:

161710

Hom.:

AF XY:

0.00428

AC XY:

365

AN XY:

85192

show subpopulations

Gnomad AFR exome

AF:

0.00186

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00593

Gnomad EAS exome

AF:

0.0129

Gnomad SAS exome

AF:

0.00330

Gnomad FIN exome

AF:

0.0000638

Gnomad NFE exome

AF:

0.00392

Gnomad OTH exome

AF:

0.00704

GnomAD4 exome

AF:

0.00436

AC:

6115

AN:

1402904

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

3070

AN XY:

692298

show subpopulations

Gnomad4 AFR exome

AF:

0.00249

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.00468

Gnomad4 EAS exome

AF:

0.0229

Gnomad4 SAS exome

AF:

0.00322

Gnomad4 FIN exome

AF:

0.000344

Gnomad4 NFE exome

AF:

0.00399

Gnomad4 OTH exome

AF:

0.00622

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152332

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0158

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00354

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00391

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.00317

AC:

ExAC

AF:

0.00229

AC:

260

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

.;D;D

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Uncertain

0.013

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-4.3

.;D;.

REVEL

Uncertain

0.53

Sift

Uncertain

0.0020

.;D;.

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.74

MVP

0.64

MPC

0.96

ClinPred

0.015

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.65

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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