NM_001166412.2:c.463+2569T>C

Variant names:

• chr6-168530296-T-C
• rs1884475
• NM_001166412.2:c.463+2569T>C

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+2569T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,148 control chromosomes in the GnomAD database, including 59,684 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 0.88 (59684 hom., cov: 32)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

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.463+2569T>C		intron	N/A	NP_001159884.1	Q9H3U7-1
	SMOC2	NM_022138.3		c.463+2569T>C		intron	N/A	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.463+2569T>C		intron	N/A	ENSP00000348630.3	Q9H3U7-1
	SMOC2	ENST00000354536.9	TSL:1	c.463+2569T>C		intron	N/A	ENSP00000346537.5	Q9H3U7-2
	SMOC2	ENST00000960304.1		c.484+2569T>C		intron	N/A	ENSP00000630363.1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133098 AN: 152030 Hom.: 59651 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.875 AC: 133188 AN: 152148 Hom.: 59684 Cov.: 32 AF XY: 0.878 AC XY: 65321 AN XY: 74372

African (AFR) AF: 0.658 AC: 27266 AN: 41452

American (AMR) AF: 0.936 AC: 14302 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3333 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5129 AN: 5164

South Asian (SAS) AF: 0.943 AC: 4538 AN: 4810

European-Finnish (FIN) AF: 0.970 AC: 10295 AN: 10610

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.959 AC: 65259 AN: 68034

Other (OTH) AF: 0.898 AC: 1898 AN: 2114

Alfa AF: 0.887 Hom.: 3850

Bravo AF: 0.864

Asia WGS AF: 0.942 AC: 3277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.30
DANN	Benign	0.41
PhyloP100		-2.4
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: rs1884475; hg19: chr6-168930976;