chr6-168515742-T-C

Variant names:

• chr6-168515742-T-C
• rs2248421
• NM_001166412.2:c.256+5656T>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.256+5656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,244 control chromosomes in the GnomAD database, including 61,939 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 0.90 (61939 hom., cov: 35)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.51
• 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, 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.256+5656T>C		intron	N/A	NP_001159884.1	Q9H3U7-1
	SMOC2	NM_022138.3		c.256+5656T>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.256+5656T>C		intron	N/A	ENSP00000348630.3	Q9H3U7-1
	SMOC2	ENST00000354536.9	TSL:1	c.256+5656T>C		intron	N/A	ENSP00000346537.5	Q9H3U7-2
	SMOC2	ENST00000960304.1		c.256+5656T>C		intron	N/A	ENSP00000630363.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136207 AN: 152126 Hom.: 61902 Cov.: 35

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.895 AC: 136298 AN: 152244 Hom.: 61939 Cov.: 35 AF XY: 0.899 AC XY: 66913 AN XY: 74456

African (AFR) AF: 0.719 AC: 29843 AN: 41504

American (AMR) AF: 0.945 AC: 14468 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3334 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5164 AN: 5170

South Asian (SAS) AF: 0.976 AC: 4719 AN: 4834

European-Finnish (FIN) AF: 0.978 AC: 10380 AN: 10612

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.960 AC: 65282 AN: 68024

Other (OTH) AF: 0.916 AC: 1939 AN: 2116

Alfa AF: 0.909 Hom.: 7321

Bravo AF: 0.885

Asia WGS AF: 0.963 AC: 3351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.024
DANN	Benign	0.24
PhyloP100		-3.5
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: rs2248421; hg19: chr6-168916422;