NM_001166412.2:c.638-20600C>T

Variant names:

• chr6-168578218-C-T
• rs753151
• NM_001166412.2:c.638-20600C>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.638-20600C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,030 control chromosomes in the GnomAD database, including 16,146 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 0.45 (16146 hom., cov: 33)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2	c.638-20600C>T		intron_variant	Intron 7 of 12	ENST00000356284.7	NP_001159884.1
SMOC2	NM_022138.3	c.671-20600C>T		intron_variant	Intron 7 of 12		NP_071421.1
SMOC2	XM_011536065.2	c.671-20600C>T		intron_variant	Intron 7 of 12		XP_011534367.1
SMOC2	XM_011536066.2	c.638-20600C>T		intron_variant	Intron 7 of 12		XP_011534368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC2	ENST00000356284.7	c.638-20600C>T		intron_variant	Intron 7 of 12	1	NM_001166412.2	ENSP00000348630.3
SMOC2	ENST00000354536.9	c.671-20600C>T		intron_variant	Intron 7 of 12	1		ENSP00000346537.5

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69058 AN: 151912 Hom.: 16137 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.454 AC: 69096 AN: 152030 Hom.: 16146 Cov.: 33 AF XY: 0.451 AC XY: 33499 AN XY: 74310

African (AFR) AF: 0.567 AC: 23506 AN: 41466

American (AMR) AF: 0.374 AC: 5715 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1694 AN: 3466

East Asian (EAS) AF: 0.498 AC: 2555 AN: 5130

South Asian (SAS) AF: 0.420 AC: 2025 AN: 4820

European-Finnish (FIN) AF: 0.368 AC: 3896 AN: 10576

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28219 AN: 67968

Other (OTH) AF: 0.442 AC: 933 AN: 2112

Alfa AF: 0.421 Hom.: 1716

Bravo AF: 0.464

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.54
PhyloP100		-0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs753151; hg19: chr6-168978898; COSMIC: COSV62435646;