dbSNP rs1049269: SPOCK2:c.*2517T>C (chr10-72060243-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001244950.2(SPOCK2):c.*2517T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,428 control chromosomes in the GnomAD database, including 32,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 32585 hom., cov: 32)

Exomes 𝑓: 0.72 ( 83 hom. )

Consequence

SPOCK2
NM_001244950.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

Publications

21 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK2	NM_001244950.2 link	c.*2517T>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000373109.7	NP_001231879.1	Q92563-1
SPOCK2	NM_014767.2 link	c.*2517T>C		3_prime_UTR_variant	Exon 12 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.*2517T>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_001244950.2	ENSP00000362201.2		Q92563-1
SPOCK2	ENST00000317376.8 link	c.*2517T>C		3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000321108.4		Q92563-1

Frequencies

GnomAD3 genomes

AF:

0.637

AC:

96805

AN:

151990

Hom.:

32549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.878

Gnomad AMI

AF:

0.560

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.630

GnomAD4 exome

AF:

0.716

AC:

229

AN:

320

Hom.:

Cov.:

AF XY:

0.708

AC XY:

187

AN XY:

264

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

0.300

AC:

AN:

South Asian (SAS)

AF:

0.667

AC:

AN:

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.720

AC:

183

AN:

254

Other (OTH)

AF:

0.650

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.637

AC:

96890

AN:

152108

Hom.:

32585

Cov.:

AF XY:

0.627

AC XY:

46642

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.877

AC:

36441

AN:

41530

American (AMR)

AF:

0.584

AC:

8925

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1781

AN:

3470

East Asian (EAS)

AF:

0.455

AC:

2347

AN:

5160

South Asian (SAS)

AF:

0.444

AC:

2134

AN:

4810

European-Finnish (FIN)

AF:

0.520

AC:

5500

AN:

10582

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.555

AC:

37745

AN:

67962

Other (OTH)

AF:

0.626

AC:

1324

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1671

3342

5012

6683

8354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.573

Hom.:

42690

Bravo

AF:

0.654

Asia WGS

AF:

0.501

AC:

1745

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.2

(source)

DANN

Benign

0.37

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over