rs1049269

chr10-72060243-A-G

Variant summary

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

The NM_001244950.2(SPOCK2):c.*2517T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,428 control chromosomes in the GnomAD database, including 32,668 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 0.64 (32585 hom., cov: 32)
  • Exomes 𝑓: 0.72 (83 hom.)
• Consequence: SPOCK2 NM_001244950.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

Genes affected

SPOCK2 (HGNC:13564): (SPARC (osteonectin), cwcv and kazal like domains proteoglycan 2) This gene encodes a protein which binds with glycosaminoglycans to form part of the extracellular matrix. The protein contains thyroglobulin type-1, follistatin-like, and calcium-binding domains, and has glycosaminoglycan attachment sites in the acidic C-terminal region. Three alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPOCK2	NM_001244950.2	c.*2517T>C		3_prime_UTR_variant	11/11	ENST00000373109.7
SPOCK2	NM_014767.2	c.*2517T>C		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPOCK2	ENST00000373109.7	c.*2517T>C		3_prime_UTR_variant	11/11	1	NM_001244950.2	P1
SPOCK2	ENST00000317376.8	c.*2517T>C		3_prime_UTR_variant	12/12	1		P1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96805 AN: 151990 Hom.: 32549 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.716 AC: 229 AN: 320 Hom.: 83 Cov.: 0 AF XY: 0.708 AC XY: 187 AN XY: 264

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.637 AC: 96890 AN: 152108 Hom.: 32585 Cov.: 32 AF XY: 0.627 AC XY: 46642 AN XY: 74332

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.626

Alfa AF: 0.562 Hom.: 32049

Bravo AF: 0.654

Asia WGS AF: 0.501 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.2
Dann	Benign	0.37

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: rs1049269; hg19: chr10-73820001;