NM_001166412.2:c.363+317T>C

Variant names:

• chr6-168526769-T-C
• rs2255680
• NM_001166412.2:c.363+317T>C

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.363+317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,016 control chromosomes in the GnomAD database, including 37,420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (37420 hom., cov: 32)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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=-0.9).
• BP6: Variant 6-168526769-T-C is Benign according to our data. Variant chr6-168526769-T-C is described in ClinVar as [Benign]. Clinvar id is 1253369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2	c.363+317T>C		intron_variant	Intron 3 of 12	ENST00000356284.7	NP_001159884.1
SMOC2	NM_022138.3	c.363+317T>C		intron_variant	Intron 3 of 12		NP_071421.1
SMOC2	XM_011536065.2	c.363+317T>C		intron_variant	Intron 3 of 12		XP_011534367.1
SMOC2	XM_011536066.2	c.363+317T>C		intron_variant	Intron 3 of 12		XP_011534368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC2	ENST00000356284.7	c.363+317T>C		intron_variant	Intron 3 of 12	1	NM_001166412.2	ENSP00000348630.3
SMOC2	ENST00000354536.9	c.363+317T>C		intron_variant	Intron 3 of 12	1		ENSP00000346537.5

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103481 AN: 151898 Hom.: 37402 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.681 AC: 103543 AN: 152016 Hom.: 37420 Cov.: 32 AF XY: 0.685 AC XY: 50858 AN XY: 74294

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.715

Alfa AF: 0.755 Hom.: 21019

Bravo AF: 0.661

Asia WGS AF: 0.733 AC: 2550 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.019
DANN	Benign	0.63

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: rs2255680; hg19: chr6-168927449;