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, PanelApp Australia, 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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166412.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC2	NM_001166412.2	MANE Select	c.72C>G	p.Phe24Leu	missense	Exon 1 of 13	NP_001159884.1	Q9H3U7-1
	SMOC2	NM_022138.3		c.72C>G	p.Phe24Leu	missense	Exon 1 of 13	NP_071421.1	Q9H3U7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMOC2	ENST00000356284.7	TSL:1 MANE Select	c.72C>G	p.Phe24Leu	missense	Exon 1 of 13	ENSP00000348630.3	Q9H3U7-1
SMOC2	ENST00000354536.9	TSL:1	c.72C>G	p.Phe24Leu	missense	Exon 1 of 13	ENSP00000346537.5	Q9H3U7-2
SMOC2	ENST00000960304.1		c.72C>G	p.Phe24Leu	missense	Exon 1 of 13	ENSP00000630363.1

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

Age Distribution

Exome Het

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:

0.0000131

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.67

M_CAP

Benign

0.039

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PhyloP100

0.36

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.36

REVEL

Benign

0.099

Sift

Benign

0.76

Sift4G

Benign

0.53

Polyphen

0.0010

Vest4

0.13

MutPred

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over