rs2144749

Positions:

• chr6-168552011-G-A
• chr6-168552011-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001166412.2(SMOC2):​c.637+2808G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,086 control chromosomes in the GnomAD database, including 40,726 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 0.72 (40726 hom., cov: 32)
• Consequence: SMOC2 NM_001166412.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMOC2	NM_001166412.2	c.637+2808G>A		intron_variant		ENST00000356284.7	NP_001159884.1
SMOC2	NM_022138.3	c.670+2808G>A		intron_variant			NP_071421.1
SMOC2	XM_011536065.2	c.670+2808G>A		intron_variant			XP_011534367.1
SMOC2	XM_011536066.2	c.637+2808G>A		intron_variant			XP_011534368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOC2	ENST00000356284.7	c.637+2808G>A		intron_variant		1	NM_001166412.2	ENSP00000348630	P3
SMOC2	ENST00000354536.9	c.670+2808G>A		intron_variant		1		ENSP00000346537	A1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108828 AN: 151968 Hom.: 40666 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.716 AC: 108947 AN: 152086 Hom.: 40726 Cov.: 32 AF XY: 0.718 AC XY: 53393 AN XY: 74324

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.697

Alfa AF: 0.645 Hom.: 15672

Bravo AF: 0.738

Asia WGS AF: 0.904 AC: 3141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.4
DANN	Benign	0.67

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: rs2144749; hg19: chr6-168952691;