chr10-72062770-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001244950.2(SPOCK2):c.1265A>G(p.Tyr422Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,605,528 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
SPOCK2
NM_001244950.2 missense
NM_001244950.2 missense
Scores
6
6
4
Clinical Significance
Conservation
PhyloP100: 7.41
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPOCK2 | NM_001244950.2 | c.1265A>G | p.Tyr422Cys | missense_variant | 11/11 | ENST00000373109.7 | |
SPOCK2 | NM_014767.2 | c.1265A>G | p.Tyr422Cys | missense_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPOCK2 | ENST00000373109.7 | c.1265A>G | p.Tyr422Cys | missense_variant | 11/11 | 1 | NM_001244950.2 | P1 | |
SPOCK2 | ENST00000317376.8 | c.1265A>G | p.Tyr422Cys | missense_variant | 12/12 | 1 | P1 | ||
SPOCK2 | ENST00000463279.6 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000413 AC: 6AN: 1453476Hom.: 0 Cov.: 72 AF XY: 0.00000138 AC XY: 1AN XY: 723502
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74268
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The c.1265A>G (p.Y422C) alteration is located in exon 12 (coding exon 11) of the SPOCK2 gene. This alteration results from a A to G substitution at nucleotide position 1265, causing the tyrosine (Y) at amino acid position 422 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
REVEL
Uncertain
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Loss of phosphorylation at Y422 (P = 0.0222);Loss of phosphorylation at Y422 (P = 0.0222);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at