chr6-168530136-G-A

Variant names:

• chr6-168530136-G-A
• rs747995
• NM_001166412.2:c.463+2409G>A

Variant summary

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

The NM_001166412.2(SMOC2):​c.463+2409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,096 control chromosomes in the GnomAD database, including 2,983 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 0.19 (2983 hom., cov: 33)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2	c.463+2409G>A		intron_variant	Intron 4 of 12	ENST00000356284.7	NP_001159884.1
SMOC2	NM_022138.3	c.463+2409G>A		intron_variant	Intron 4 of 12		NP_071421.1
SMOC2	XM_011536065.2	c.463+2409G>A		intron_variant	Intron 4 of 12		XP_011534367.1
SMOC2	XM_011536066.2	c.463+2409G>A		intron_variant	Intron 4 of 12		XP_011534368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC2	ENST00000356284.7	c.463+2409G>A		intron_variant	Intron 4 of 12	1	NM_001166412.2	ENSP00000348630.3
SMOC2	ENST00000354536.9	c.463+2409G>A		intron_variant	Intron 4 of 12	1		ENSP00000346537.5

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29053 AN: 151978 Hom.: 2978 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.191 AC: 29082 AN: 152096 Hom.: 2983 Cov.: 33 AF XY: 0.191 AC XY: 14165 AN XY: 74346

African (AFR) AF: 0.232 AC: 9638 AN: 41456

American (AMR) AF: 0.246 AC: 3762 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 779 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1184 AN: 5160

South Asian (SAS) AF: 0.188 AC: 906 AN: 4822

European-Finnish (FIN) AF: 0.160 AC: 1696 AN: 10574

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10596 AN: 68014

Other (OTH) AF: 0.181 AC: 383 AN: 2112

Alfa AF: 0.183 Hom.: 521

Bravo AF: 0.200

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.78
PhyloP100		-1.9
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: rs747995; hg19: chr6-168930816;