20-1312422-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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

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:):

FKBP1A-SDCBP2 links:

Genome browser will be placed here

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
SDCBP2	NM_080489.5 linkuse as main transcript	c.647T>G	p.Val216Gly	missense_variant	7/9	ENST00000360779.4
FKBP1A-SDCBP2	NR_037661.1 linkuse as main transcript	n.925T>G		non_coding_transcript_exon_variant	8/10
SDCBP2	NM_001199784.2 linkuse as main transcript	c.647T>G	p.Val216Gly	missense_variant	7/9
SDCBP2	NM_015685.6 linkuse as main transcript	c.392T>G	p.Val131Gly	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDCBP2	ENST00000360779.4 linkuse as main transcript	c.647T>G	p.Val216Gly	missense_variant	7/9	1	NM_080489.5	P1	Q9H190-1
SDCBP2	ENST00000339987.7 linkuse as main transcript	c.647T>G	p.Val216Gly	missense_variant	7/9	1		P1	Q9H190-1
SDCBP2	ENST00000381808.7 linkuse as main transcript	c.392T>G	p.Val131Gly	missense_variant	3/5	1			Q9H190-3
SDCBP2	ENST00000381812.5 linkuse as main transcript	c.647T>G	p.Val216Gly	missense_variant	7/9	5		P1	Q9H190-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.92

M_CAP

Uncertain

0.098

MetaRNN

Uncertain

0.53

D;D;D;D

MetaSVM

Benign

-0.70

MutationAssessor

Pathogenic

3.2

M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.7

D;D;D;D

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.98

D;.;D;D

Vest4

0.48

MutPred

0.68

Loss of stability (P = 0.0012);.;Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);

MVP

0.46

MPC

0.71

ClinPred

1.0

GERP RS

3.6

Varity_R

0.88

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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