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GeneBe

10-72067017-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001244950.2(SPOCK2):c.813C>T(p.Ala271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,614,212 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 16 hom., cov: 32)
Exomes 𝑓: 0.00078 ( 13 hom. )

Consequence

SPOCK2
NM_001244950.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.13
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-72067017-G-A is Benign according to our data. Variant chr10-72067017-G-A is described in ClinVar as [Benign]. Clinvar id is 780138.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.13 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0078 (1188/152338) while in subpopulation AFR AF= 0.0262 (1090/41570). AF 95% confidence interval is 0.0249. There are 16 homozygotes in gnomad4. There are 513 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 16 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPOCK2NM_001244950.2 linkuse as main transcriptc.813C>T p.Ala271= synonymous_variant 8/11 ENST00000373109.7
SPOCK2NM_014767.2 linkuse as main transcriptc.813C>T p.Ala271= synonymous_variant 9/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPOCK2ENST00000373109.7 linkuse as main transcriptc.813C>T p.Ala271= synonymous_variant 8/111 NM_001244950.2 P1Q92563-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00779
AC:
1186
AN:
152220
Hom.:
16
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0262
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00432
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.00198
AC:
498
AN:
251452
Hom.:
3
AF XY:
0.00146
AC XY:
198
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.0266
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000149
Gnomad OTH exome
AF:
0.000977
GnomAD4 exome
AF:
0.000775
AC:
1133
AN:
1461874
Hom.:
13
Cov.:
32
AF XY:
0.000677
AC XY:
492
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0268
Gnomad4 AMR exome
AF:
0.00123
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000585
Gnomad4 OTH exome
AF:
0.00162
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00780
AC:
1188
AN:
152338
Hom.:
16
Cov.:
32
AF XY:
0.00689
AC XY:
513
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0262
Gnomad4 AMR
AF:
0.00431
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00757
Alfa
AF:
0.00470
Hom.:
1
Bravo
AF:
0.00881
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.23
Dann
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs7079142; hg19: chr10-73826775; API