20-1310458-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_080489.5(SDCBP2):c.862T>C(p.Ser288Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
SDCBP2
NM_080489.5 missense
NM_080489.5 missense
Scores
2
10
6
Clinical Significance
Conservation
PhyloP100: 3.46
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.17268595).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDCBP2 | NM_080489.5 | c.862T>C | p.Ser288Pro | missense_variant | 9/9 | ENST00000360779.4 | |
FKBP1A-SDCBP2 | NR_037661.1 | n.1140T>C | non_coding_transcript_exon_variant | 10/10 | |||
SDCBP2 | NM_001199784.2 | c.862T>C | p.Ser288Pro | missense_variant | 9/9 | ||
SDCBP2 | NM_015685.6 | c.607T>C | p.Ser203Pro | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDCBP2 | ENST00000360779.4 | c.862T>C | p.Ser288Pro | missense_variant | 9/9 | 1 | NM_080489.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250700Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135626
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461236Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8AN XY: 726944
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74326
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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 | Sep 16, 2021 | The c.862T>C (p.S288P) alteration is located in exon 9 (coding exon 8) of the SDCBP2 gene. This alteration results from a T to C substitution at nucleotide position 862, causing the serine (S) at amino acid position 288 to be replaced by a proline (P). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;D;D
Vest4
MVP
MPC
0.75
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