20-1310812-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_080489.5(SDCBP2):c.812A>C(p.His271Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDCBP2 NM_080489.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDCBP2	NM_080489.5	c.812A>C	p.His271Pro	missense_variant	8/9	ENST00000360779.4
FKBP1A-SDCBP2	NR_037661.1	n.1090A>C		non_coding_transcript_exon_variant	9/10
SDCBP2	NM_001199784.2	c.812A>C	p.His271Pro	missense_variant	8/9
SDCBP2	NM_015685.6	c.557A>C	p.His186Pro	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDCBP2	ENST00000360779.4	c.812A>C	p.His271Pro	missense_variant	8/9	1	NM_080489.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

The c.812A>C (p.H271P) alteration is located in exon 8 (coding exon 7) of the SDCBP2 gene. This alteration results from a A to C substitution at nucleotide position 812, causing the histidine (H) at amino acid position 271 to be replaced by a proline (P). 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	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
Cadd	Pathogenic	28
Dann	Uncertain	0.98
DEOGEN2	Benign	0.28	T;.;T;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.1	M;.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-9.1	D;D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.90
MutPred		0.59		Gain of relative solvent accessibility (P = 0.0999);.;Gain of relative solvent accessibility (P = 0.0999);Gain of relative solvent accessibility (P = 0.0999);
MVP		0.46
MPC		0.85
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.93
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1291456;