6-168441442-C-G

Variant names:

Variant summary

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

The NM_001166412.2(SMOC2):c.72C>G(p.Phe24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000597 in 1,508,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

SMOC2
NM_001166412.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.356

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

SMOC2 links:

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=0.05005476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2 link	c.72C>G	p.Phe24Leu	missense_variant	Exon 1 of 13	ENST00000356284.7	NP_001159884.1	Q9H3U7-1
SMOC2	NM_022138.3 link	c.72C>G	p.Phe24Leu	missense_variant	Exon 1 of 13		NP_071421.1	Q9H3U7-2
SMOC2	XM_011536065.2 link	c.72C>G	p.Phe24Leu	missense_variant	Exon 1 of 13		XP_011534367.1
SMOC2	XM_011536066.2 link	c.72C>G	p.Phe24Leu	missense_variant	Exon 1 of 13		XP_011534368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC2	ENST00000356284.7 link	c.72C>G	p.Phe24Leu	missense_variant	Exon 1 of 13	1	NM_001166412.2	ENSP00000348630.3		Q9H3U7-1
SMOC2	ENST00000354536.9 link	c.72C>G	p.Phe24Leu	missense_variant	Exon 1 of 13	1		ENSP00000346537.5		Q9H3U7-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000289

AC:

AN:

103632

AF XY:

0.0000174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000516

AC:

AN:

1355938

Hom.:

Cov.:

AF XY:

0.00000299

AC XY:

AN XY:

668408

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27336

American (AMR)

AF:

0.000189

AC:

AN:

31754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24048

East Asian (EAS)

AF:

0.00

AC:

AN:

30428

South Asian (SAS)

AF:

0.00

AC:

AN:

75586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

9.40e-7

AC:

AN:

1064290

Other (OTH)

AF:

0.00

AC:

AN:

56308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.000131

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.72C>G (p.F24L) alteration is located in exon 1 (coding exon 1) of the SMOC2 gene. This alteration results from a C to G substitution at nucleotide position 72, causing the phenylalanine (F) at amino acid position 24 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

N;N

PhyloP100

0.36

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.099

Sift

Benign

0.76

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.0010

B;B

Vest4

0.13

MutPred

0.28

Loss of methylation at K23 (P = 0.0289);Loss of methylation at K23 (P = 0.0289);

MVP

0.21

MPC

0.17

ClinPred

0.046

GERP RS

3.5

PromoterAI

-0.021

Neutral

(source)

Varity_R

0.061

gMVP

0.36

Mutation Taster

=84/16

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

6-168441442-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over