rs1042381

Positions:

• chr8-96602433-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002998.4(SDC2):​c.211T>A​(p.Ser71Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,613,670 control chromosomes in the GnomAD database, including 32,186 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (4968 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27218 hom.)
• Consequence: SDC2 NM_002998.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.31

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001964897).
• BP6: Variant 8-96602433-T-A is Benign according to our data. Variant chr8-96602433-T-A is described in ClinVar as [Benign]. Clinvar id is 1288543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC2	NM_002998.4	c.211T>A	p.Ser71Thr	missense_variant	3/5	ENST00000302190.9
SDC2	XM_011517212.4	c.124T>A	p.Ser42Thr	missense_variant	4/6
SDC2	XM_024447228.2	c.124T>A	p.Ser42Thr	missense_variant	4/6
SDC2	XM_047422076.1	c.124T>A	p.Ser42Thr	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC2	ENST00000302190.9	c.211T>A	p.Ser71Thr	missense_variant	3/5	1	NM_002998.4	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35940 AN: 151978 Hom.: 4958 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.220

GnomAD3 exomes AF: 0.180 AC: 45104 AN: 251260 Hom.: 4664 AF XY: 0.175 AC XY: 23807 AN XY: 135778

Gnomad AFR exome AF: 0.392

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.187 AC: 274033 AN: 1461574 Hom.: 27218 Cov.: 32 AF XY: 0.185 AC XY: 134630 AN XY: 727116

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.237 AC: 35977 AN: 152096 Hom.: 4968 Cov.: 32 AF XY: 0.230 AC XY: 17136 AN XY: 74356

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.220

Alfa AF: 0.192 Hom.: 2315

Bravo AF: 0.246

TwinsUK AF: 0.187 AC: 694

ALSPAC AF: 0.205 AC: 789

ESP6500AA AF: 0.380 AC: 1674

ESP6500EA AF: 0.182 AC: 1568

ExAC AF: 0.185 AC: 22441

Asia WGS AF: 0.187 AC: 654 AN: 3478

EpiCase AF: 0.190

EpiControl AF: 0.181

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 24, 2019	This variant is associated with the following publications: (PMID: 24442880) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;.;.;.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.52	T;T;.;T;T;T
MetaRNN	Benign	0.0020	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M;.;.;.;.;.
MutationTaster	Benign	0.024	P;P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.74	N;N;N;N;N;N
REVEL	Benign	0.077
Sift	Benign	0.27	T;T;T;T;T;T
Sift4G	Benign	0.62	T;T;T;T;T;T
Polyphen		0.72	P;.;.;.;.;.
Vest4		0.18
MPC		0.42
ClinPred		0.0094	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.047
gMVP		0.24

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: rs1042381; hg19: chr8-97614661; COSMIC: COSV56226598;