6-168509763-C-G

Variant names:

• chr6-168509763-C-G
• rs2749256
• NM_001166412.2:c.85-152C>G

Variant summary

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

The NM_001166412.2(SMOC2):​c.85-152C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 587,674 control chromosomes in the GnomAD database, including 43,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9273 hom., cov: 33)
  • Exomes 𝑓: 0.38 (33960 hom.)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-168509763-C-G is Benign according to our data. Variant chr6-168509763-C-G is described in ClinVar as [Benign]. Clinvar id is 1280242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2	c.85-152C>G		intron_variant	Intron 1 of 12	ENST00000356284.7	NP_001159884.1
SMOC2	NM_022138.3	c.85-152C>G		intron_variant	Intron 1 of 12		NP_071421.1
SMOC2	XM_011536065.2	c.85-152C>G		intron_variant	Intron 1 of 12		XP_011534367.1
SMOC2	XM_011536066.2	c.85-152C>G		intron_variant	Intron 1 of 12		XP_011534368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC2	ENST00000356284.7	c.85-152C>G		intron_variant	Intron 1 of 12	1	NM_001166412.2	ENSP00000348630.3
SMOC2	ENST00000354536.9	c.85-152C>G		intron_variant	Intron 1 of 12	1		ENSP00000346537.5

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51000 AN: 151976 Hom.: 9275 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.385 AC: 167637 AN: 435580 Hom.: 33960 AF XY: 0.389 AC XY: 86665 AN XY: 223042

African (AFR) AF: 0.190 AC: 2494 AN: 13136

American (AMR) AF: 0.302 AC: 4737 AN: 15682

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 4858 AN: 12202

East Asian (EAS) AF: 0.451 AC: 13740 AN: 30440

South Asian (SAS) AF: 0.468 AC: 11333 AN: 24226

European-Finnish (FIN) AF: 0.290 AC: 7919 AN: 27338

Middle Eastern (MID) AF: 0.405 AC: 737 AN: 1820

European-Non Finnish (NFE) AF: 0.393 AC: 112509 AN: 286428

Other (OTH) AF: 0.383 AC: 9310 AN: 24308

GnomAD4 genome AF: 0.335 AC: 50990 AN: 152094 Hom.: 9273 Cov.: 33 AF XY: 0.333 AC XY: 24723 AN XY: 74332

African (AFR) AF: 0.202 AC: 8364 AN: 41490

American (AMR) AF: 0.317 AC: 4842 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1414 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2688 AN: 5154

South Asian (SAS) AF: 0.492 AC: 2369 AN: 4818

European-Finnish (FIN) AF: 0.292 AC: 3084 AN: 10572

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27122 AN: 67986

Other (OTH) AF: 0.359 AC: 759 AN: 2114

Alfa AF: 0.210 Hom.: 471

Bravo AF: 0.329

Asia WGS AF: 0.467 AC: 1621 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.39
PhyloP100		-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: rs2749256; hg19: chr6-168910443;