rs1042381

Variant names:

• chr8-96602433-T-A
• rs1042381
• NM_002998.4:c.211T>A

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002998.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC2	NM_002998.4	MANE Select	c.211T>A	p.Ser71Thr	missense	Exon 3 of 5	NP_002989.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC2	ENST00000302190.9	TSL:1 MANE Select	c.211T>A	p.Ser71Thr	missense	Exon 3 of 5	ENSP00000307046.4	P34741
	SDC2	ENST00000862192.1		c.211T>A	p.Ser71Thr	missense	Exon 3 of 5	ENSP00000532251.1
	SDC2	ENST00000932834.1		c.211T>A	p.Ser71Thr	missense	Exon 4 of 6	ENSP00000602893.1

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

GnomAD2 exomes AF: 0.180 AC: 45104 AN: 251260 AF XY: 0.175

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 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

African (AFR) AF: 0.395 AC: 13225 AN: 33472

American (AMR) AF: 0.110 AC: 4901 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4459 AN: 26130

East Asian (EAS) AF: 0.202 AC: 7999 AN: 39694

South Asian (SAS) AF: 0.132 AC: 11368 AN: 86250

European-Finnish (FIN) AF: 0.155 AC: 8297 AN: 53416

Middle Eastern (MID) AF: 0.182 AC: 1050 AN: 5768

European-Non Finnish (NFE) AF: 0.190 AC: 211159 AN: 1111744

Other (OTH) AF: 0.192 AC: 11575 AN: 60382

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

African (AFR) AF: 0.385 AC: 15966 AN: 41434

American (AMR) AF: 0.166 AC: 2545 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3466

East Asian (EAS) AF: 0.224 AC: 1158 AN: 5174

South Asian (SAS) AF: 0.149 AC: 719 AN: 4818

European-Finnish (FIN) AF: 0.157 AC: 1666 AN: 10596

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12684 AN: 67994

Other (OTH) AF: 0.220 AC: 465 AN: 2114

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.13
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.077
Sift	Benign	0.27	T
Sift4G	Benign	0.62	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
Mutation Taster		=87/13	polymorphism (auto)

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

Other links and lift over

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