NM_001166412.2:c.908-19873C>T

Variant names:

• chr6-168630808-C-T
• rs9456259
• NM_001166412.2:c.908-19873C>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.908-19873C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,118 control chromosomes in the GnomAD database, including 2,286 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 0.17 (2286 hom., cov: 33)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 2 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, 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2	c.908-19873C>T		intron_variant	Intron 9 of 12	ENST00000356284.7	NP_001159884.1
SMOC2	NM_022138.3	c.941-19873C>T		intron_variant	Intron 9 of 12		NP_071421.1
SMOC2	XM_011536065.2	c.941-19873C>T		intron_variant	Intron 9 of 12		XP_011534367.1
SMOC2	XM_011536066.2	c.908-19873C>T		intron_variant	Intron 9 of 12		XP_011534368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC2	ENST00000356284.7	c.908-19873C>T		intron_variant	Intron 9 of 12	1	NM_001166412.2	ENSP00000348630.3
SMOC2	ENST00000354536.9	c.941-19873C>T		intron_variant	Intron 9 of 12	1		ENSP00000346537.5

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25650 AN: 151996 Hom.: 2286 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.169 AC: 25657 AN: 152118 Hom.: 2286 Cov.: 33 AF XY: 0.171 AC XY: 12710 AN XY: 74366

African (AFR) AF: 0.179 AC: 7434 AN: 41492

American (AMR) AF: 0.171 AC: 2616 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3470

East Asian (EAS) AF: 0.151 AC: 781 AN: 5174

South Asian (SAS) AF: 0.286 AC: 1378 AN: 4816

European-Finnish (FIN) AF: 0.139 AC: 1472 AN: 10574

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10398 AN: 67978

Other (OTH) AF: 0.201 AC: 425 AN: 2114

Alfa AF: 0.156 Hom.: 281

Bravo AF: 0.169

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.64
DANN	Benign	0.59
PhyloP100		0.055
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: rs9456259; hg19: chr6-169031488; COSMIC: COSV62443600;