6-168441433-T-G

Variant names:

• chr6-168441433-T-G
• rs73270928
• NM_001166412.2:c.63T>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001166412.2(SMOC2):​c.63T>G​(p.Ala21Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,507,100 control chromosomes in the GnomAD database, including 36,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (8327 hom., cov: 33)
  • Exomes 𝑓: 0.18 (28424 hom.)
• Consequence: SMOC2 NM_001166412.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.212
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 6-168441433-T-G is Benign according to our data. Variant chr6-168441433-T-G is described in ClinVar as Benign. ClinVar VariationId is 1257770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.212 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

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.63T>G	p.Ala21Ala	synonymous	Exon 1 of 13	NP_001159884.1	Q9H3U7-1
	SMOC2	NM_022138.3		c.63T>G	p.Ala21Ala	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.63T>G	p.Ala21Ala	synonymous	Exon 1 of 13	ENSP00000348630.3	Q9H3U7-1
	SMOC2	ENST00000354536.9	TSL:1	c.63T>G	p.Ala21Ala	synonymous	Exon 1 of 13	ENSP00000346537.5	Q9H3U7-2
	SMOC2	ENST00000960304.1		c.63T>G	p.Ala21Ala	synonymous	Exon 1 of 13	ENSP00000630363.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44154 AN: 151866 Hom.: 8315 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.253

GnomAD2 exomes AF: 0.242 AC: 25101 AN: 103790 AF XY: 0.242

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.346

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.398

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.183 AC: 248438 AN: 1355128 Hom.: 28424 Cov.: 32 AF XY: 0.187 AC XY: 125250 AN XY: 668024

African (AFR) AF: 0.532 AC: 14520 AN: 27318

American (AMR) AF: 0.330 AC: 10426 AN: 31562

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4586 AN: 24054

East Asian (EAS) AF: 0.433 AC: 13146 AN: 30386

South Asian (SAS) AF: 0.367 AC: 27691 AN: 75434

European-Finnish (FIN) AF: 0.132 AC: 5536 AN: 41908

Middle Eastern (MID) AF: 0.215 AC: 891 AN: 4142

European-Non Finnish (NFE) AF: 0.150 AC: 159830 AN: 1064082

Other (OTH) AF: 0.210 AC: 11812 AN: 56242

GnomAD4 genome AF: 0.291 AC: 44193 AN: 151972 Hom.: 8327 Cov.: 33 AF XY: 0.293 AC XY: 21756 AN XY: 74258

African (AFR) AF: 0.522 AC: 21651 AN: 41480

American (AMR) AF: 0.292 AC: 4470 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3468

East Asian (EAS) AF: 0.454 AC: 2311 AN: 5090

South Asian (SAS) AF: 0.374 AC: 1803 AN: 4820

European-Finnish (FIN) AF: 0.143 AC: 1514 AN: 10592

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.162 AC: 10984 AN: 67918

Other (OTH) AF: 0.254 AC: 536 AN: 2110

Alfa AF: 0.202 Hom.: 1145

Bravo AF: 0.310

Asia WGS AF: 0.456 AC: 1578 AN: 3458

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		-0.21
PromoterAI		-0.022	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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: rs73270928; hg19: chr6-168842113; COSMIC: COSV62439696;