Genetic Variant SDCBP2:p.Arg185Leu (chr20-1312593-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080489.5(SDCBP2):c.554G>T(p.Arg185Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R185Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

SDCBP2
NM_080489.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.13

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.911

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080489.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDCBP2	NM_080489.5	MANE Select	c.554G>T	p.Arg185Leu	missense	Exon 6 of 9	NP_536737.3
SDCBP2	NM_001199784.2		c.554G>T	p.Arg185Leu	missense	Exon 6 of 9	NP_001186713.1	Q9H190-1
SDCBP2	NM_015685.6		c.299G>T	p.Arg100Leu	missense	Exon 2 of 5	NP_056500.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDCBP2	ENST00000360779.4	TSL:1 MANE Select	c.554G>T	p.Arg185Leu	missense	Exon 6 of 9	ENSP00000354013.3	Q9H190-1
SDCBP2	ENST00000339987.7	TSL:1	c.554G>T	p.Arg185Leu	missense	Exon 6 of 9	ENSP00000342935.3	Q9H190-1
SDCBP2	ENST00000381808.7	TSL:1	c.299G>T	p.Arg100Leu	missense	Exon 2 of 5	ENSP00000371229.3	Q9H190-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

0.43

MutationAssessor

Pathogenic

3.0

PhyloP100

6.1

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-7.0

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.94

MutPred

0.64

Loss of MoRF binding (P = 0.0236)

MVP

0.90

MPC

0.75

ClinPred

1.0

GERP RS

4.5

Varity_R

0.87

gMVP

0.75

Mutation Taster

=19/81

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over