6-168441430-C-G

Variant names:

• chr6-168441430-C-G
• rs553730194
• NM_001166412.2:c.60C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

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
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.406
• Publications: 0 publications found

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

ACMG classification

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 VariationId is 2075464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.406 with no splicing effect.

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.60C>G	p.Pro20Pro	synonymous	Exon 1 of 13	NP_001159884.1	Q9H3U7-1
	SMOC2	NM_022138.3		c.60C>G	p.Pro20Pro	synonymous	Exon 1 of 13	NP_071421.1	Q9H3U7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC2	ENST00000356284.7	TSL:1 MANE Select	c.60C>G	p.Pro20Pro	synonymous	Exon 1 of 13	ENSP00000348630.3	Q9H3U7-1
	SMOC2	ENST00000354536.9	TSL:1	c.60C>G	p.Pro20Pro	synonymous	Exon 1 of 13	ENSP00000346537.5	Q9H3U7-2
	SMOC2	ENST00000960304.1		c.60C>G	p.Pro20Pro	synonymous	Exon 1 of 13	ENSP00000630363.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152136 Hom.: 0 Cov.: 33

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

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

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

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74424

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000174

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SMOC2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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

Other links and lift over

dbSNP: rs553730194; hg19: chr6-168842110;