NM_001244950.2:c.1057G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★★).

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

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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. GnomAdExome4 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 GnomAdExome4. There are 3070 alleles in the male GnomAdExome4 subpopulation. Median coverage is 75. This position passed quality control check.

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

GnomAD2 exomes

AF:

0.00412

AC:

666

AN:

161710

AF XY:

0.00428

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 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

African (AFR)

AF:

0.00249

AC:

AN:

31716

American (AMR)

AF:

0.00279

AC:

101

AN:

36258

Ashkenazi Jewish (ASJ)

AF:

0.00468

AC:

118

AN:

25202

East Asian (EAS)

AF:

0.0229

AC:

821

AN:

35924

South Asian (SAS)

AF:

0.00322

AC:

256

AN:

79460

European-Finnish (FIN)

AF:

0.000344

AC:

AN:

49490

Middle Eastern (MID)

AF:

0.00789

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00399

AC:

4316

AN:

1080974

Other (OTH)

AF:

0.00622

AC:

362

AN:

58174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

426

852

1277

1703

2129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152332

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

41578

American (AMR)

AF:

0.00399

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.0158

AC:

AN:

5186

South Asian (SAS)

AF:

0.00435

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00354

AC:

241

AN:

68026

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00399

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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;.

PhyloP100

7.8

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

Mutation Taster

=99/1

polymorphism

(source)

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

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NM_001244950.2:c.1057G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over