6-168441334-A-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.-37A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,493,822 control chromosomes in the GnomAD database, including 36,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (8329 hom., cov: 33)
  • Exomes 𝑓: 0.18 (28175 hom.)
• Consequence: SMOC2 NM_001166412.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.130

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=-0.77).
• BP6: Variant 6-168441334-A-G is Benign according to our data. Variant chr6-168441334-A-G is described in ClinVar as [Benign]. Clinvar id is 1233812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC2	NM_001166412.2	c.-37A>G		5_prime_UTR_variant	1/13	ENST00000356284.7
SMOC2	NM_022138.3	c.-37A>G		5_prime_UTR_variant	1/13
SMOC2	XM_011536065.2	c.-37A>G		5_prime_UTR_variant	1/13
SMOC2	XM_011536066.2	c.-37A>G		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC2	ENST00000356284.7	c.-37A>G		5_prime_UTR_variant	1/13	1	NM_001166412.2	P3
SMOC2	ENST00000354536.9	c.-37A>G		5_prime_UTR_variant	1/13	1		A1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44146 AN: 151780 Hom.: 8317 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.254

GnomAD3 exomes AF: 0.252 AC: 23304 AN: 92560 Hom.: 3631 AF XY: 0.251 AC XY: 13093 AN XY: 52110

Gnomad AFR exome AF: 0.473

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.409

Gnomad SAS exome AF: 0.356

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.184 AC: 246443 AN: 1341936 Hom.: 28175 Cov.: 32 AF XY: 0.188 AC XY: 124331 AN XY: 661834

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.291 AC: 44182 AN: 151886 Hom.: 8329 Cov.: 33 AF XY: 0.293 AC XY: 21749 AN XY: 74238

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.255

Alfa AF: 0.215 Hom.: 813

Bravo AF: 0.310

Asia WGS AF: 0.455 AC: 1576 AN: 3462

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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	13
Dann	Benign	0.76

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: rs76776636; hg19: chr6-168842014; COSMIC: COSV62440806;