6-168526769-T-C

Variant names:

• chr6-168526769-T-C
• rs2255680
• NM_001166412.2:c.363+317T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022138.3(SMOC2):​c.363+317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,016 control chromosomes in the GnomAD database, including 37,420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (37420 hom., cov: 32)
• Consequence: SMOC2 NM_022138.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48
• 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, 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-168526769-T-C is Benign according to our data. Variant chr6-168526769-T-C is described in ClinVar as Benign. ClinVar VariationId is 1253369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022138.3. 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.363+317T>C		intron	N/A	NP_001159884.1
	SMOC2	NM_022138.3		c.363+317T>C		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.363+317T>C		intron	N/A	ENSP00000348630.3
	SMOC2	ENST00000354536.9	TSL:1	c.363+317T>C		intron	N/A	ENSP00000346537.5
	SMOC2	ENST00000960304.1		c.384+296T>C		intron	N/A	ENSP00000630363.1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103481 AN: 151898 Hom.: 37402 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.681 AC: 103543 AN: 152016 Hom.: 37420 Cov.: 32 AF XY: 0.685 AC XY: 50858 AN XY: 74294

African (AFR) AF: 0.417 AC: 17269 AN: 41392

American (AMR) AF: 0.689 AC: 10533 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2556 AN: 3472

East Asian (EAS) AF: 0.764 AC: 3946 AN: 5162

South Asian (SAS) AF: 0.728 AC: 3494 AN: 4802

European-Finnish (FIN) AF: 0.810 AC: 8573 AN: 10586

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54634 AN: 68004

Other (OTH) AF: 0.715 AC: 1508 AN: 2108

Alfa AF: 0.755 Hom.: 23485

Bravo AF: 0.661

Asia WGS AF: 0.733 AC: 2550 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.019
DANN	Benign	0.63
PhyloP100		-1.5
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: rs2255680; hg19: chr6-168927449;