6-168621373-C-T

Variant names:

• chr6-168621373-C-T
• rs12197584
• NM_001166412.2:c.907+13134C>T

Variant summary

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

The NM_001166412.2(SMOC2):​c.907+13134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,134 control chromosomes in the GnomAD database, including 4,348 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 0.23 (4348 hom., cov: 33)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 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.907+13134C>T		intron	N/A	NP_001159884.1	Q9H3U7-1
	SMOC2	NM_022138.3		c.940+13134C>T		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.907+13134C>T		intron	N/A	ENSP00000348630.3	Q9H3U7-1
	SMOC2	ENST00000354536.9	TSL:1	c.940+13134C>T		intron	N/A	ENSP00000346537.5	Q9H3U7-2
	SMOC2	ENST00000960304.1		c.961+13134C>T		intron	N/A	ENSP00000630363.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35697 AN: 152016 Hom.: 4338 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.235 AC: 35733 AN: 152134 Hom.: 4348 Cov.: 33 AF XY: 0.236 AC XY: 17534 AN XY: 74354

African (AFR) AF: 0.198 AC: 8212 AN: 41518

American (AMR) AF: 0.215 AC: 3295 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3468

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5178

South Asian (SAS) AF: 0.193 AC: 927 AN: 4804

European-Finnish (FIN) AF: 0.300 AC: 3173 AN: 10562

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17594 AN: 67986

Other (OTH) AF: 0.204 AC: 430 AN: 2112

Alfa AF: 0.244 Hom.: 19374

Bravo AF: 0.228

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		0.43
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: rs12197584; hg19: chr6-169022053;