20-1312603-C-T

Position:

• chr20-1312603-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080489.5(SDCBP2):​c.544G>A​(p.Val182Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,613,434 control chromosomes in the GnomAD database, including 173,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (14261 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158749 hom.)
• Consequence: SDCBP2 NM_080489.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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]

FKBP1A-SDCBP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032036602).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDCBP2	NM_080489.5	c.544G>A	p.Val182Met	missense_variant	6/9	ENST00000360779.4
FKBP1A-SDCBP2	NR_037661.1	n.822G>A		non_coding_transcript_exon_variant	7/10
SDCBP2	NM_001199784.2	c.544G>A	p.Val182Met	missense_variant	6/9
SDCBP2	NM_015685.6	c.289G>A	p.Val97Met	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDCBP2	ENST00000360779.4	c.544G>A	p.Val182Met	missense_variant	6/9	1	NM_080489.5	P1
SDCBP2	ENST00000339987.7	c.544G>A	p.Val182Met	missense_variant	6/9	1		P1
SDCBP2	ENST00000381808.7	c.289G>A	p.Val97Met	missense_variant	2/5	1
SDCBP2	ENST00000381812.5	c.544G>A	p.Val182Met	missense_variant	6/9	5		P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64418 AN: 151878 Hom.: 14251 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.455

GnomAD3 exomes AF: 0.392 AC: 98434 AN: 251066 Hom.: 21626 AF XY: 0.397 AC XY: 53844 AN XY: 135700

Gnomad AFR exome AF: 0.409

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.531

Gnomad EAS exome AF: 0.0912

Gnomad SAS exome AF: 0.315

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.442

GnomAD4 exome AF: 0.458 AC: 669083 AN: 1461438 Hom.: 158749 Cov.: 73 AF XY: 0.455 AC XY: 330876 AN XY: 726928

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.445

GnomAD4 genome AF: 0.424 AC: 64466 AN: 151996 Hom.: 14261 Cov.: 32 AF XY: 0.414 AC XY: 30767 AN XY: 74304

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.0962

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.452

Alfa AF: 0.471 Hom.: 42914

Bravo AF: 0.428

TwinsUK AF: 0.495 AC: 1834

ALSPAC AF: 0.488 AC: 1880

ESP6500AA AF: 0.406 AC: 1791

ESP6500EA AF: 0.491 AC: 4225

ExAC AF: 0.396 AC: 48022

Asia WGS AF: 0.222 AC: 772 AN: 3478

EpiCase AF: 0.498

EpiControl AF: 0.503

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.71
DEOGEN2	Benign	0.014	T;.;T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.75	.;T;.;T
MetaRNN	Benign	0.0032	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.1	N;.;N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.1	N;N;N;N
REVEL	Benign	0.055
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.75	T;T;T;T
Polyphen		0.0010	B;.;B;B
Vest4		0.027
MPC		0.16
ClinPred		0.0040	T
GERP RS		4.5
Varity_R		0.037
gMVP		0.19

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

Other links and lift over

dbSNP: rs2273959; hg19: chr20-1293247; COSMIC: COSV60588226; COSMIC: COSV60588226;