rs1232314

Variant names:

• chr6-168488625-A-G
• rs1232314
• NM_001166412.2:c.85-21290A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001166412.2(SMOC2):​c.85-21290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,258 control chromosomes in the GnomAD database, including 2,465 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2465 hom., cov: 33)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 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.85-21290A>G		intron	N/A	NP_001159884.1	Q9H3U7-1
	SMOC2	NM_022138.3		c.85-21290A>G		intron	N/A	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.85-21290A>G		intron	N/A	ENSP00000348630.3	Q9H3U7-1
	SMOC2	ENST00000354536.9	TSL:1	c.85-21290A>G		intron	N/A	ENSP00000346537.5	Q9H3U7-2
	SMOC2	ENST00000960304.1		c.85-21290A>G		intron	N/A	ENSP00000630363.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24523 AN: 152140 Hom.: 2461 Cov.: 33

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.161 AC: 24524 AN: 152258 Hom.: 2465 Cov.: 33 AF XY: 0.161 AC XY: 12008 AN XY: 74430

African (AFR) AF: 0.0469 AC: 1949 AN: 41578

American (AMR) AF: 0.136 AC: 2082 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 650 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1703 AN: 5160

South Asian (SAS) AF: 0.183 AC: 884 AN: 4830

European-Finnish (FIN) AF: 0.195 AC: 2067 AN: 10598

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14472 AN: 68002

Other (OTH) AF: 0.196 AC: 414 AN: 2116

Alfa AF: 0.199 Hom.: 5683

Bravo AF: 0.154

Asia WGS AF: 0.245 AC: 852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.34
DANN	Benign	0.67
PhyloP100		-0.75
Mutation Taster		=100/0	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: rs1232314; hg19: chr6-168889305;