20-1313450-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080489.5(SDCBP2):c.274G>C(p.Gly92Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000136 in 1,600,518 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 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SDCBP2
NM_080489.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49

Variant links:

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]

SDCBP2 links:

FKBP1A-SDCBP2 (HGNC:41997): (FKBP1A-SDCBP2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring FK506 binding protein 1A, 12kDa and syndecan binding protein (syntenin) 2 genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

FKBP1A-SDCBP2 links:

Genome browser will be placed here

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, 0.854

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCBP2	NM_080489.5 link	c.274G>C	p.Gly92Arg	missense_variant	Exon 5 of 9	ENST00000360779.4	NP_536737.3	Q9H190-1
SDCBP2	NM_001199784.2 link	c.274G>C	p.Gly92Arg	missense_variant	Exon 5 of 9		NP_001186713.1	Q9H190-1
SDCBP2	NM_015685.6 link	c.19G>C	p.Gly7Arg	missense_variant	Exon 1 of 5		NP_056500.2	Q9H190-3
FKBP1A-SDCBP2	NR_037661.1 link	n.552G>C		non_coding_transcript_exon_variant	Exon 6 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCBP2	ENST00000360779.4 link	c.274G>C	p.Gly92Arg	missense_variant	Exon 5 of 9	1	NM_080489.5	ENSP00000354013.3		Q9H190-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000579

AC:

AN:

224350

Hom.:

AF XY:

0.0000654

AC XY:

AN XY:

122268

show subpopulations

Gnomad AFR exome

AF:

0.0000732

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000355

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000992

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.000135

AC:

196

AN:

1448296

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

719726

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000172

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.000138

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000251

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.274G>C (p.G92R) alteration is located in exon 5 (coding exon 4) of the SDCBP2 gene. This alteration results from a G to C substitution at nucleotide position 274, causing the glycine (G) at amino acid position 92 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.97

.;D;.;D

M_CAP

Benign

0.060

MetaRNN

Pathogenic

0.85

D;D;D;D

MetaSVM

Benign

-0.41

MutationAssessor

Pathogenic

3.2

M;.;M;M

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-6.8

D;D;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.88

MutPred

0.72

Gain of MoRF binding (P = 0.0073);.;Gain of MoRF binding (P = 0.0073);Gain of MoRF binding (P = 0.0073);

MVP

0.66

MPC

0.70

ClinPred

0.86

GERP RS

4.2

Varity_R

0.64

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over