rs1048621

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080489.5(SDCBP2):c.667C>T(p.Arg223Cys) variant causes a missense change. The variant allele was found at a frequency of 0.252 in 1,612,836 control chromosomes in the GnomAD database, including 54,492 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 3935 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50557 hom. )

Consequence

SDCBP2
NM_080489.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.05

Publications

31 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002702564).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

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
SDCBP2	NM_080489.5	MANE Select	c.667C>T	p.Arg223Cys	missense	Exon 7 of 9	NP_536737.3
SDCBP2	NM_001199784.2		c.667C>T	p.Arg223Cys	missense	Exon 7 of 9	NP_001186713.1
SDCBP2	NM_015685.6		c.412C>T	p.Arg138Cys	missense	Exon 3 of 5	NP_056500.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SDCBP2	ENST00000360779.4	TSL:1 MANE Select	c.667C>T	p.Arg223Cys	missense	Exon 7 of 9	ENSP00000354013.3
SDCBP2	ENST00000339987.7	TSL:1	c.667C>T	p.Arg223Cys	missense	Exon 7 of 9	ENSP00000342935.3
SDCBP2	ENST00000381808.7	TSL:1	c.412C>T	p.Arg138Cys	missense	Exon 3 of 5	ENSP00000371229.3

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33339

AN:

152012

Hom.:

3937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.0174

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.226

GnomAD2 exomes

AF:

0.204

AC:

50596

AN:

248036

AF XY:

0.206

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.0169

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.255

AC:

372562

AN:

1460706

Hom.:

50557

Cov.:

AF XY:

0.252

AC XY:

183066

AN XY:

726538

show subpopulations

African (AFR)

AF:

0.169

AC:

5671

AN:

33464

American (AMR)

AF:

0.171

AC:

7640

AN:

44562

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

5781

AN:

26114

East Asian (EAS)

AF:

0.0126

AC:

498

AN:

39668

South Asian (SAS)

AF:

0.134

AC:

11562

AN:

86156

European-Finnish (FIN)

AF:

0.200

AC:

10681

AN:

53286

Middle Eastern (MID)

AF:

0.164

AC:

948

AN:

5766

European-Non Finnish (NFE)

AF:

0.284

AC:

315742

AN:

1111356

Other (OTH)

AF:

0.233

AC:

14039

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

16196

32392

48588

64784

80980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10366

20732

31098

41464

51830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.219

AC:

33342

AN:

152130

Hom.:

3935

Cov.:

AF XY:

0.215

AC XY:

15960

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.170

AC:

7076

AN:

41512

American (AMR)

AF:

0.210

AC:

3215

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

767

AN:

3470

East Asian (EAS)

AF:

0.0174

AC:

AN:

5166

South Asian (SAS)

AF:

0.130

AC:

629

AN:

4826

European-Finnish (FIN)

AF:

0.196

AC:

2079

AN:

10598

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18651

AN:

67954

Other (OTH)

AF:

0.223

AC:

471

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1303

2606

3908

5211

6514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.255

Hom.:

7183

Bravo

AF:

0.218

TwinsUK

AF:

0.286

AC:

1060

ALSPAC

AF:

0.292

AC:

1124

ESP6500AA

AF:

0.167

AC:

737

ESP6500EA

AF:

0.270

AC:

2320

ExAC

AF:

0.202

AC:

24547

Asia WGS

AF:

0.0720

AC:

252

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

PhyloP100

4.0

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-7.6

REVEL

Benign

0.21

Sift

Uncertain

0.012

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.26

MPC

0.79

ClinPred

0.072

GERP RS

2.8

Varity_R

0.35

gMVP

0.60

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over