rs753149

Variant names:

• chr6-168579235-G-A
• rs753149
• NM_001166412.2:c.638-19583G>A

Variant summary

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

The ENST00000356284.7(SMOC2):​c.638-19583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 149,926 control chromosomes in the GnomAD database, including 1,378 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 0.10 (1378 hom., cov: 34)
• Consequence: SMOC2 ENST00000356284.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356284.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC2	NM_001166412.2	MANE Select	c.638-19583G>A		intron	N/A	NP_001159884.1
	SMOC2	NM_022138.3		c.671-19583G>A		intron	N/A	NP_071421.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC2	ENST00000356284.7	TSL:1 MANE Select	c.638-19583G>A		intron	N/A	ENSP00000348630.3
	SMOC2	ENST00000354536.9	TSL:1	c.671-19583G>A		intron	N/A	ENSP00000346537.5

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15470 AN: 149806 Hom.: 1383 Cov.: 34

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0390

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.103 AC: 15471 AN: 149926 Hom.: 1378 Cov.: 34 AF XY: 0.102 AC XY: 7460 AN XY: 73144

African (AFR) AF: 0.243 AC: 9884 AN: 40720

American (AMR) AF: 0.0424 AC: 634 AN: 14964

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 96 AN: 3432

East Asian (EAS) AF: 0.185 AC: 944 AN: 5104

South Asian (SAS) AF: 0.0686 AC: 320 AN: 4666

European-Finnish (FIN) AF: 0.0368 AC: 382 AN: 10380

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0443 AC: 2986 AN: 67398

Other (OTH) AF: 0.0820 AC: 170 AN: 2072

Alfa AF: 0.0724 Hom.: 88

Bravo AF: 0.110

Asia WGS AF: 0.111 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.73
PhyloP100		-1.1
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: rs753149; hg19: chr6-168979915; COSMIC: COSV107410453;