20-1313486-C-T

Variant names:

• chr20-1313486-C-T
• rs745940961
• NM_080489.5:c.238G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080489.5(SDCBP2):​c.238G>A​(p.Gly80Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000202 in 1,438,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: SDCBP2 NM_080489.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.381

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052657425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCBP2	NM_080489.5	c.238G>A	p.Gly80Ser	missense_variant	Exon 5 of 9	ENST00000360779.4	NP_536737.3
SDCBP2	NM_001199784.2	c.238G>A	p.Gly80Ser	missense_variant	Exon 5 of 9		NP_001186713.1
SDCBP2	NM_015685.6	c.-18G>A		5_prime_UTR_variant	Exon 1 of 5		NP_056500.2
FKBP1A-SDCBP2	NR_037661.1	n.516G>A		non_coding_transcript_exon_variant	Exon 6 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCBP2	ENST00000360779.4	c.238G>A	p.Gly80Ser	missense_variant	Exon 5 of 9	1	NM_080489.5	ENSP00000354013.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000527 AC: 11 AN: 208584 Hom.: 0 AF XY: 0.0000525 AC XY: 6 AN XY: 114392

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.000191

GnomAD4 exome AF: 0.0000202 AC: 29 AN: 1438554 Hom.: 0 Cov.: 31 AF XY: 0.0000140 AC XY: 10 AN XY: 714382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000223

Gnomad4 NFE exome AF: 0.0000244

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000227

ExAC AF: 0.000108 AC: 13

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238G>A (p.G80S) alteration is located in exon 5 (coding exon 4) of the SDCBP2 gene. This alteration results from a G to A substitution at nucleotide position 238, causing the glycine (G) at amino acid position 80 to be replaced by a serine (S). 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	0.072
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.83
DEOGEN2	Benign	0.012	T;T;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.48	.;.;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.70	N;N;N
REVEL	Benign	0.024
Sift	Benign	0.75	T;T;T
Sift4G	Benign	0.77	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.28
MVP		0.25
MPC		0.17
ClinPred		0.044	T
GERP RS		2.2
Varity_R		0.027
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs745940961; hg19: chr20-1294130;