6-168441430-C-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001166412.2(SMOC2):​c.60C>G​(p.Pro20Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,510,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SMOC2
NM_001166412.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.406

Publications

0 publications found
Variant links:
Genes affected
SMOC2 (HGNC:20323): (SPARC related modular calcium binding 2) This gene encodes a member of the SPARC family (secreted protein acidic and rich in cysteine/osteonectin/BM-40), which are highly expressed during embryogenesis and wound healing. The gene product is a matricellular protein which promotes matrix assembly and can stimulate endothelial cell proliferation and migration, as well as angiogenic activity. Associated with pulmonary function, this secretory gene product contains a Kazal domain, two thymoglobulin type-1 domains, and two EF-hand calcium-binding domains. The encoded protein may serve as a target for controlling angiogenesis in tumor growth and myocardial ischemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
SMOC2 Gene-Disease associations (from GenCC):
  • dentin dysplasia type I
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
  • atypical dentin dysplasia due to SMOC2 deficiency
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 6-168441430-C-G is Benign according to our data. Variant chr6-168441430-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2075464.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.406 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMOC2NM_001166412.2 linkc.60C>G p.Pro20Pro synonymous_variant Exon 1 of 13 ENST00000356284.7 NP_001159884.1 Q9H3U7-1
SMOC2NM_022138.3 linkc.60C>G p.Pro20Pro synonymous_variant Exon 1 of 13 NP_071421.1 Q9H3U7-2
SMOC2XM_011536065.2 linkc.60C>G p.Pro20Pro synonymous_variant Exon 1 of 13 XP_011534367.1
SMOC2XM_011536066.2 linkc.60C>G p.Pro20Pro synonymous_variant Exon 1 of 13 XP_011534368.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMOC2ENST00000356284.7 linkc.60C>G p.Pro20Pro synonymous_variant Exon 1 of 13 1 NM_001166412.2 ENSP00000348630.3 Q9H3U7-1
SMOC2ENST00000354536.9 linkc.60C>G p.Pro20Pro synonymous_variant Exon 1 of 13 1 ENSP00000346537.5 Q9H3U7-2

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152136
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00144
GnomAD2 exomes
AF:
0.000217
AC:
23
AN:
105830
AF XY:
0.000137
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000442
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000286
Gnomad OTH exome
AF:
0.000965
GnomAD4 exome
AF:
0.000162
AC:
220
AN:
1358188
Hom.:
0
Cov.:
32
AF XY:
0.000158
AC XY:
106
AN XY:
669596
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
27450
American (AMR)
AF:
0.000527
AC:
17
AN:
32238
Ashkenazi Jewish (ASJ)
AF:
0.0000415
AC:
1
AN:
24124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30788
South Asian (SAS)
AF:
0.00
AC:
0
AN:
75824
European-Finnish (FIN)
AF:
0.0000951
AC:
4
AN:
42054
Middle Eastern (MID)
AF:
0.00265
AC:
11
AN:
4156
European-Non Finnish (NFE)
AF:
0.000146
AC:
155
AN:
1065138
Other (OTH)
AF:
0.000567
AC:
32
AN:
56416
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.487
Heterozygous variant carriers
0
13
25
38
50
63
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<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:
0.000158
AC:
24
AN:
152244
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74424
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41578
American (AMR)
AF:
0.000327
AC:
5
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5130
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.0137
AC:
4
AN:
292
European-Non Finnish (NFE)
AF:
0.000162
AC:
11
AN:
67992
Other (OTH)
AF:
0.00142
AC:
3
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.540
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.000174

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 29, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

SMOC2-related disorder Benign:1
Apr 11, 2019
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
8.0
DANN
Benign
0.67
PhyloP100
-0.41
PromoterAI
0.027
Neutral
Mutation Taster
=100/0
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: rs553730194; hg19: chr6-168842110; API