rs1245560

Positions:

• chr10-72077662-A-C

Variant summary

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

The NM_001244950.2(SPOCK2):​c.190-4752T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,992 control chromosomes in the GnomAD database, including 19,669 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 0.51 (19669 hom., cov: 32)
• Consequence: SPOCK2 NM_001244950.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.855

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=-0.48).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK2	NM_001244950.2	c.190-4752T>G		intron_variant		ENST00000373109.7	NP_001231879.1
SPOCK2	NM_014767.2	c.190-4752T>G		intron_variant			NP_055582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPOCK2	ENST00000373109.7	c.190-4752T>G		intron_variant		1	NM_001244950.2	ENSP00000362201	P1
SPOCK2	ENST00000317376.8	c.190-4752T>G		intron_variant		1		ENSP00000321108	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77081 AN: 151874 Hom.: 19664 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.507 AC: 77122 AN: 151992 Hom.: 19669 Cov.: 32 AF XY: 0.503 AC XY: 37365 AN XY: 74284

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.497

Alfa AF: 0.492 Hom.: 24135

Bravo AF: 0.513

Asia WGS AF: 0.418 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.92

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: rs1245560; hg19: chr10-73837420;