rs2273959

Variant names:

• chr20-1312603-C-T
• rs2273959
• NM_080489.5:c.544G>A
• SDCBP2 p.Val182Met

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 38 publications found

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: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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCBP2	NM_080489.5	MANE Select	c.544G>A	p.Val182Met	missense	Exon 6 of 9	NP_536737.3
	SDCBP2	NM_001199784.2		c.544G>A	p.Val182Met	missense	Exon 6 of 9	NP_001186713.1	Q9H190-1
	SDCBP2	NM_015685.6		c.289G>A	p.Val97Met	missense	Exon 2 of 5	NP_056500.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCBP2	ENST00000360779.4	TSL:1 MANE Select	c.544G>A	p.Val182Met	missense	Exon 6 of 9	ENSP00000354013.3	Q9H190-1
	SDCBP2	ENST00000339987.7	TSL:1	c.544G>A	p.Val182Met	missense	Exon 6 of 9	ENSP00000342935.3	Q9H190-1
	SDCBP2	ENST00000381808.7	TSL:1	c.289G>A	p.Val97Met	missense	Exon 2 of 5	ENSP00000371229.3	Q9H190-3

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

GnomAD2 exomes AF: 0.392 AC: 98434 AN: 251066 AF XY: 0.397

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 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

African (AFR) AF: 0.404 AC: 13524 AN: 33468

American (AMR) AF: 0.311 AC: 13921 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 13944 AN: 26132

East Asian (EAS) AF: 0.120 AC: 4773 AN: 39694

South Asian (SAS) AF: 0.318 AC: 27462 AN: 86250

European-Finnish (FIN) AF: 0.331 AC: 17679 AN: 53390

Middle Eastern (MID) AF: 0.476 AC: 2744 AN: 5762

European-Non Finnish (NFE) AF: 0.493 AC: 548158 AN: 1111668

Other (OTH) AF: 0.445 AC: 26878 AN: 60370

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

African (AFR) AF: 0.404 AC: 16759 AN: 41436

American (AMR) AF: 0.391 AC: 5984 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1837 AN: 3468

East Asian (EAS) AF: 0.0962 AC: 496 AN: 5158

South Asian (SAS) AF: 0.310 AC: 1493 AN: 4816

European-Finnish (FIN) AF: 0.323 AC: 3413 AN: 10572

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32909 AN: 67946

Other (OTH) AF: 0.452 AC: 952 AN: 2108

Alfa AF: 0.465 Hom.: 75790

Bravo AF: 0.428

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 v4.9

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
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.1	N
PhyloP100		2.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.055
Sift	Benign	1.0	T
Sift4G	Benign	0.75	T
Varity_R		0.037
gMVP		0.19
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2273959;

hg19: chr20-1293247;

COSMIC: COSV60588226;

COSMIC: COSV60588226;