6-168441334-A-G

Variant names:

• chr6-168441334-A-G
• rs76776636
• NM_001166412.2:c.-37A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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, G2P, Labcorp Genetics (formerly Invitae)
• atypical dentin dysplasia due to SMOC2 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2	c.-37A>G		5_prime_UTR_variant	Exon 1 of 13	ENST00000356284.7	NP_001159884.1
SMOC2	NM_022138.3	c.-37A>G		5_prime_UTR_variant	Exon 1 of 13		NP_071421.1
SMOC2	XM_011536065.2	c.-37A>G		5_prime_UTR_variant	Exon 1 of 13		XP_011534367.1
SMOC2	XM_011536066.2	c.-37A>G		5_prime_UTR_variant	Exon 1 of 13		XP_011534368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC2	ENST00000356284.7	c.-37A>G		5_prime_UTR_variant	Exon 1 of 13	1	NM_001166412.2	ENSP00000348630.3
SMOC2	ENST00000354536.9	c.-37A>G		5_prime_UTR_variant	Exon 1 of 13	1		ENSP00000346537.5

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

GnomAD2 exomes AF: 0.252 AC: 23304 AN: 92560 AF XY: 0.251

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 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

African (AFR) AF: 0.532 AC: 14399 AN: 27056

American (AMR) AF: 0.329 AC: 10202 AN: 30974

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4527 AN: 23772

East Asian (EAS) AF: 0.434 AC: 12842 AN: 29580

South Asian (SAS) AF: 0.367 AC: 27537 AN: 75082

European-Finnish (FIN) AF: 0.139 AC: 4808 AN: 34512

Middle Eastern (MID) AF: 0.219 AC: 868 AN: 3962

European-Non Finnish (NFE) AF: 0.150 AC: 159549 AN: 1061172

Other (OTH) AF: 0.210 AC: 11711 AN: 55826

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

African (AFR) AF: 0.522 AC: 21635 AN: 41454

American (AMR) AF: 0.292 AC: 4460 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2320 AN: 5090

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4822

European-Finnish (FIN) AF: 0.143 AC: 1515 AN: 10586

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.162 AC: 10981 AN: 67882

Other (OTH) AF: 0.255 AC: 538 AN: 2112

Alfa AF: 0.223 Hom.: 910

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

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	-0.77
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		-0.13
PromoterAI		-0.038	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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