6-168441430-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001166412.2(SMOC2):c.60C>G(p.Pro20=) 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

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.406

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.406 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMOC2	NM_001166412.2 linkuse as main transcript	c.60C>G	p.Pro20=	synonymous_variant	1/13	ENST00000356284.7
SMOC2	NM_022138.3 linkuse as main transcript	c.60C>G	p.Pro20=	synonymous_variant	1/13
SMOC2	XM_011536065.2 linkuse as main transcript	c.60C>G	p.Pro20=	synonymous_variant	1/13
SMOC2	XM_011536066.2 linkuse as main transcript	c.60C>G	p.Pro20=	synonymous_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC2	ENST00000356284.7 linkuse as main transcript	c.60C>G	p.Pro20=	synonymous_variant	1/13	1	NM_001166412.2	P3	Q9H3U7-1
SMOC2	ENST00000354536.9 linkuse as main transcript	c.60C>G	p.Pro20=	synonymous_variant	1/13	1		A1	Q9H3U7-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152136

Hom.:

Cov.:

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

GnomAD3 exomes

AF:

0.000217

AC:

AN:

105830

Hom.:

AF XY:

0.000137

AC XY:

AN XY:

58592

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 SAS 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.:

Cov.:

AF XY:

0.000158

AC XY:

106

AN XY:

669596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000527

Gnomad4 ASJ exome

AF:

0.0000415

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000951

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.000567

GnomAD4 genome

AF:

0.000158

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00142

Bravo

AF:

0.000174

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 29, 2022

- -

SMOC2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 11, 2019

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over