20-1311725-C-T

Position:

• chr20-1311725-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.732+612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,078 control chromosomes in the GnomAD database, including 42,378 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 0.74 (42378 hom., cov: 31)
• Consequence: SDCBP2 NM_080489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDCBP2	NM_080489.5	c.732+612G>A		intron_variant		ENST00000360779.4
FKBP1A-SDCBP2	NR_037661.1	n.1010+612G>A		intron_variant, non_coding_transcript_variant
SDCBP2	NM_001199784.2	c.732+612G>A		intron_variant
SDCBP2	NM_015685.6	c.477+612G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDCBP2	ENST00000360779.4	c.732+612G>A		intron_variant		1	NM_080489.5	P1
SDCBP2	ENST00000339987.7	c.732+612G>A		intron_variant		1		P1
SDCBP2	ENST00000381808.7	c.477+612G>A		intron_variant		1
SDCBP2	ENST00000381812.5	c.732+612G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112473 AN: 151960 Hom.: 42367 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.734

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.740 AC: 112518 AN: 152078 Hom.: 42378 Cov.: 31 AF XY: 0.747 AC XY: 55541 AN XY: 74346

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.735

Alfa AF: 0.760 Hom.: 5512

Bravo AF: 0.726

Asia WGS AF: 0.843 AC: 2932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs6104890; hg19: chr20-1292369;