chr20-1312395-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_080489.5(SDCBP2):c.674G>T(p.Gly225Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,613,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
SDCBP2
NM_080489.5 missense
NM_080489.5 missense
Scores
11
6
1
Clinical Significance
Conservation
PhyloP100: 7.84
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.913
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDCBP2 | NM_080489.5 | c.674G>T | p.Gly225Val | missense_variant | 7/9 | ENST00000360779.4 | |
FKBP1A-SDCBP2 | NR_037661.1 | n.952G>T | non_coding_transcript_exon_variant | 8/10 | |||
SDCBP2 | NM_001199784.2 | c.674G>T | p.Gly225Val | missense_variant | 7/9 | ||
SDCBP2 | NM_015685.6 | c.419G>T | p.Gly140Val | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDCBP2 | ENST00000360779.4 | c.674G>T | p.Gly225Val | missense_variant | 7/9 | 1 | NM_080489.5 | P1 | |
SDCBP2 | ENST00000339987.7 | c.674G>T | p.Gly225Val | missense_variant | 7/9 | 1 | P1 | ||
SDCBP2 | ENST00000381808.7 | c.419G>T | p.Gly140Val | missense_variant | 3/5 | 1 | |||
SDCBP2 | ENST00000381812.5 | c.674G>T | p.Gly225Val | missense_variant | 7/9 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152178Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000105 AC: 26AN: 248494Hom.: 1 AF XY: 0.000119 AC XY: 16AN XY: 134630
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GnomAD4 exome AF: 0.000102 AC: 149AN: 1461152Hom.: 0 Cov.: 61 AF XY: 0.000114 AC XY: 83AN XY: 726818
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GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74350
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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 | Mar 25, 2022 | The c.674G>T (p.G225V) alteration is located in exon 7 (coding exon 6) of the SDCBP2 gene. This alteration results from a G to T substitution at nucleotide position 674, causing the glycine (G) at amino acid position 225 to be replaced by a valine (V). 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
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;.;D;D
Vest4
MVP
MPC
0.76
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at