rs1782967928

Variant names:

• chr6-168509982-C-G
• rs1782967928
• NM_001166412.2:c.152C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-168509982-C-G
• chr6-168509982-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001166412.2(SMOC2):​c.152C>G​(p.Pro51Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P51L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SMOC2 NM_001166412.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.84
• Publications: 0 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, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• atypical dentin dysplasia due to SMOC2 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.92

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166412.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC2	NM_001166412.2	MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 2 of 13	NP_001159884.1	Q9H3U7-1
	SMOC2	NM_022138.3		c.152C>G	p.Pro51Arg	missense	Exon 2 of 13	NP_071421.1	Q9H3U7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC2	ENST00000356284.7	TSL:1 MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 2 of 13	ENSP00000348630.3	Q9H3U7-1
	SMOC2	ENST00000354536.9	TSL:1	c.152C>G	p.Pro51Arg	missense	Exon 2 of 13	ENSP00000346537.5	Q9H3U7-2
	SMOC2	ENST00000960304.1		c.152C>G	p.Pro51Arg	missense	Exon 2 of 13	ENSP00000630363.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		6.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.93	P
Vest4		0.57
MutPred		0.88		Gain of MoRF binding (P = 0.059)
MVP		0.46
MPC		0.58
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.68
gMVP		0.86
Mutation Taster		=52/48	polymorphism

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: rs1782967928; hg19: chr6-168910662;