6-168672861-C-T

Variant names:

• chr6-168672861-C-T
• rs196450
• ENST00000477998.1:n.130-352C>T

Variant summary

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

The ENST00000477998.1(SMOC2):​n.130-352C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,976 control chromosomes in the GnomAD database, including 16,384 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 0.42 (16384 hom., cov: 32)
• Consequence: SMOC2 ENST00000477998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• 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, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• atypical dentin dysplasia due to SMOC2 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124901467 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000477998.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC2	ENST00000477998.1	TSL:3	n.130-352C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64599 AN: 151858 Hom.: 16400 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.425 AC: 64574 AN: 151976 Hom.: 16384 Cov.: 32 AF XY: 0.425 AC XY: 31552 AN XY: 74276

African (AFR) AF: 0.135 AC: 5603 AN: 41466

American (AMR) AF: 0.443 AC: 6759 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1822 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1663 AN: 5144

South Asian (SAS) AF: 0.479 AC: 2303 AN: 4806

European-Finnish (FIN) AF: 0.543 AC: 5718 AN: 10536

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38976 AN: 67968

Other (OTH) AF: 0.460 AC: 971 AN: 2112

Alfa AF: 0.477 Hom.: 2568

Bravo AF: 0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.034
PhyloP100		-2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs196450;

hg19: chr6-169073400;