6-168509763-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001166412.2(SMOC2):c.85-152C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 587,674 control chromosomes in the GnomAD database, including 43,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9273 hom., cov: 33)
  • Exomes 𝑓: 0.38 (33960 hom.)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-168509763-C-G is Benign according to our data. Variant chr6-168509763-C-G is described in ClinVar as [Benign]. Clinvar id is 1280242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC2	NM_001166412.2	c.85-152C>G		intron_variant		ENST00000356284.7
SMOC2	NM_022138.3	c.85-152C>G		intron_variant
SMOC2	XM_011536065.2	c.85-152C>G		intron_variant
SMOC2	XM_011536066.2	c.85-152C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC2	ENST00000356284.7	c.85-152C>G		intron_variant		1	NM_001166412.2	P3
SMOC2	ENST00000354536.9	c.85-152C>G		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51000 AN: 151976 Hom.: 9275 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.385 AC: 167637 AN: 435580 Hom.: 33960 AF XY: 0.389 AC XY: 86665 AN XY: 223042

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.383

GnomAD4 genome AF: 0.335 AC: 50990 AN: 152094 Hom.: 9273 Cov.: 33 AF XY: 0.333 AC XY: 24723 AN XY: 74332

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.359

Alfa AF: 0.210 Hom.: 471

Bravo AF: 0.329

Asia WGS AF: 0.467 AC: 1621 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.17
Dann	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs2749256; hg19: chr6-168910443;