chr20-1312422-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_080489.5(SDCBP2):c.647T>G(p.Val216Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,804 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: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
SDCBP2
NM_080489.5 missense
NM_080489.5 missense
Scores
5
8
5
Clinical Significance
Conservation
PhyloP100: 3.21
Genes affected
SDCBP2 (HGNC:15756): (syndecan binding protein 2) The protein encoded by this gene contains two class II PDZ domains. PDZ domains facilitate protein-protein interactions by binding to the cytoplasmic C-terminus of transmembrane proteins, and PDZ-containing proteins mediate cell signaling and the organization of protein complexes. The encoded protein binds to phosphatidylinositol 4, 5-bisphosphate (PIP2) and plays a role in nuclear PIP2 organization and cell division. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Read-through transcription also exists between this gene and the upstream FKBP1A (FK506 binding protein 1A, 12kDa) gene, as represented in GeneID:100528031. [provided by RefSeq, Sep 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 |
---|---|---|---|---|---|---|---|
SDCBP2 | NM_080489.5 | c.647T>G | p.Val216Gly | missense_variant | 7/9 | ENST00000360779.4 | |
FKBP1A-SDCBP2 | NR_037661.1 | n.925T>G | non_coding_transcript_exon_variant | 8/10 | |||
SDCBP2 | NM_001199784.2 | c.647T>G | p.Val216Gly | missense_variant | 7/9 | ||
SDCBP2 | NM_015685.6 | c.392T>G | p.Val131Gly | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDCBP2 | ENST00000360779.4 | c.647T>G | p.Val216Gly | missense_variant | 7/9 | 1 | NM_080489.5 | P1 | |
SDCBP2 | ENST00000339987.7 | c.647T>G | p.Val216Gly | missense_variant | 7/9 | 1 | P1 | ||
SDCBP2 | ENST00000381808.7 | c.392T>G | p.Val131Gly | missense_variant | 3/5 | 1 | |||
SDCBP2 | ENST00000381812.5 | c.647T>G | p.Val216Gly | missense_variant | 7/9 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461676Hom.: 0 Cov.: 63 AF XY: 0.00000550 AC XY: 4AN XY: 727120
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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 | Apr 04, 2023 | The c.647T>G (p.V216G) alteration is located in exon 7 (coding exon 6) of the SDCBP2 gene. This alteration results from a T to G substitution at nucleotide position 647, causing the valine (V) at amino acid position 216 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;.;D;D
Vest4
MutPred
Loss of stability (P = 0.0012);.;Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);
MVP
MPC
0.71
ClinPred
D
GERP RS
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