10-72063045-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001244950.2(SPOCK2):​c.1109C>A​(p.Thr370Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000257 in 1,553,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T370M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPOCK2
NM_001244950.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.167

Publications

0 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.040655524).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPOCK2NM_001244950.2 linkc.1109C>A p.Thr370Lys missense_variant Exon 10 of 11 ENST00000373109.7 NP_001231879.1 Q92563-1
SPOCK2NM_014767.2 linkc.1109C>A p.Thr370Lys missense_variant Exon 11 of 12 NP_055582.1 Q92563-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPOCK2ENST00000373109.7 linkc.1109C>A p.Thr370Lys missense_variant Exon 10 of 11 1 NM_001244950.2 ENSP00000362201.2 Q92563-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1401550
Hom.:
0
Cov.:
74
AF XY:
0.00
AC XY:
0
AN XY:
691636
show subpopulations
African (AFR)
AF:
0.0000316
AC:
1
AN:
31684
American (AMR)
AF:
0.00
AC:
0
AN:
36052
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25192
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35874
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79440
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49140
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5694
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1080350
Other (OTH)
AF:
0.0000172
AC:
1
AN:
58124
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152310
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74478
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000241
AC:
1
AN:
41570
American (AMR)
AF:
0.00
AC:
0
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68026
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.002339), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
0.11
DANN
Benign
0.39
DEOGEN2
Benign
0.095
T;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.084
N
LIST_S2
Benign
0.77
.;T;T
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.041
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.1
L;L;.
PhyloP100
0.17
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.3
.;N;.
REVEL
Benign
0.10
Sift
Benign
0.79
.;T;.
Sift4G
Benign
0.73
T;T;T
Polyphen
0.35
B;B;.
Vest4
0.16
MutPred
0.50
Gain of ubiquitination at T370 (P = 0.0045);Gain of ubiquitination at T370 (P = 0.0045);.;
MVP
0.17
MPC
0.36
ClinPred
0.15
T
GERP RS
-2.9
Varity_R
0.081
gMVP
0.69
Mutation Taster
=93/7
polymorphism

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

Other links and lift over

dbSNP: rs564644987; hg19: chr10-73822803; API