rs3816208

Positions:

• chr8-96602397-G-A

Variant summary

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

The ENST00000302190.9(SDC2):​c.175G>A​(p.Ala59Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,613,172 control chromosomes in the GnomAD database, including 5,753 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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 0.065 (459 hom., cov: 32)
  • Exomes 𝑓: 0.076 (5294 hom.)
• Consequence: SDC2 ENST00000302190.9 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36

Genes affected

SDC2 (HGNC:10659): (syndecan 2) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-2 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-2 expression has been detected in several different tumor types. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016243458).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC2	NM_002998.4	c.175G>A	p.Ala59Thr	missense_variant, splice_region_variant	3/5	ENST00000302190.9	NP_002989.2
SDC2	XM_011517212.4	c.88G>A	p.Ala30Thr	missense_variant, splice_region_variant	4/6		XP_011515514.1
SDC2	XM_024447228.2	c.88G>A	p.Ala30Thr	missense_variant, splice_region_variant	4/6		XP_024302996.1
SDC2	XM_047422076.1	c.88G>A	p.Ala30Thr	missense_variant, splice_region_variant	3/5		XP_047278032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC2	ENST00000302190.9	c.175G>A	p.Ala59Thr	missense_variant, splice_region_variant	3/5	1	NM_002998.4	ENSP00000307046	P1

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9937 AN: 152126 Hom.: 460 Cov.: 32

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0771

GnomAD3 exomes AF: 0.0969 AC: 24282 AN: 250620 Hom.: 1696 AF XY: 0.0936 AC XY: 12674 AN XY: 135422

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.0587

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.115

Gnomad FIN exome AF: 0.0941

Gnomad NFE exome AF: 0.0613

Gnomad OTH exome AF: 0.0812

GnomAD4 exome AF: 0.0758 AC: 110741 AN: 1460928 Hom.: 5294 Cov.: 30 AF XY: 0.0759 AC XY: 55163 AN XY: 726744

Gnomad4 AFR exome AF: 0.0218

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.0552

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0913

Gnomad4 NFE exome AF: 0.0655

Gnomad4 OTH exome AF: 0.0802

GnomAD4 genome AF: 0.0653 AC: 9942 AN: 152244 Hom.: 459 Cov.: 32 AF XY: 0.0688 AC XY: 5122 AN XY: 74440

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0963

Gnomad4 NFE AF: 0.0630

Gnomad4 OTH AF: 0.0782

Alfa AF: 0.0687 Hom.: 997

Bravo AF: 0.0663

TwinsUK AF: 0.0682 AC: 253

ALSPAC AF: 0.0724 AC: 279

ESP6500AA AF: 0.0281 AC: 124

ESP6500EA AF: 0.0652 AC: 561

ExAC AF: 0.0917 AC: 11139

Asia WGS AF: 0.168 AC: 583 AN: 3478

EpiCase AF: 0.0634

EpiControl AF: 0.0628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.13	T;.;.;.;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.025
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	T;T;.;T;T;T
MetaRNN	Benign	0.0016	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.;.;.;.;.
MutationTaster	Benign	0.0031	P;P;P;P;P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.57	N;N;N;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.45	T;D;T;T;T;T
Sift4G	Benign	0.41	T;T;T;T;T;T
Polyphen		0.018	B;.;.;.;.;.
Vest4		0.065
MPC		0.25
ClinPred		0.029	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.22

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: rs3816208; hg19: chr8-97614625; COSMIC: COSV56229985;