6-168441442-C-T

Variant names:

• chr6-168441442-C-T
• rs1378774701
• NM_001166412.2:c.72C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001166412.2(SMOC2):​c.72C>T​(p.Phe24Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,355,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SMOC2 NM_001166412.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=0.356 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2	c.72C>T	p.Phe24Phe	synonymous_variant	Exon 1 of 13	ENST00000356284.7	NP_001159884.1
SMOC2	NM_022138.3	c.72C>T	p.Phe24Phe	synonymous_variant	Exon 1 of 13		NP_071421.1
SMOC2	XM_011536065.2	c.72C>T	p.Phe24Phe	synonymous_variant	Exon 1 of 13		XP_011534367.1
SMOC2	XM_011536066.2	c.72C>T	p.Phe24Phe	synonymous_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.72C>T	p.Phe24Phe	synonymous_variant	Exon 1 of 13	1	NM_001166412.2	ENSP00000348630.3
SMOC2	ENST00000354536.9	c.72C>T	p.Phe24Phe	synonymous_variant	Exon 1 of 13	1		ENSP00000346537.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1355938 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 668408

African (AFR) AF: 0.00 AC: 0 AN: 27336

American (AMR) AF: 0.00 AC: 0 AN: 31754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24048

East Asian (EAS) AF: 0.00 AC: 0 AN: 30428

South Asian (SAS) AF: 0.00 AC: 0 AN: 75586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1064290

Other (OTH) AF: 0.00 AC: 0 AN: 56308

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.7
DANN	Benign	0.95
PhyloP100		0.36
PromoterAI		-0.039	Neutral

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: rs1378774701; hg19: chr6-168842122;