rs2028086

Variant names:

• chr8-96591950-G-C
• rs2028086
• NM_002998.4:c.61-1530G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002998.4(SDC2):​c.61-1530G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,086 control chromosomes in the GnomAD database, including 3,246 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 0.19 (3246 hom., cov: 32)
• Consequence: SDC2 NM_002998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC2	NM_002998.4	c.61-1530G>C		intron_variant	Intron 1 of 4	ENST00000302190.9	NP_002989.2
SDC2	XM_011517212.4	c.-27-1530G>C		intron_variant	Intron 2 of 5		XP_011515514.1
SDC2	XM_024447228.2	c.-27-1530G>C		intron_variant	Intron 2 of 5		XP_024302996.1
SDC2	XM_047422076.1	c.-27-1530G>C		intron_variant	Intron 1 of 4		XP_047278032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC2	ENST00000302190.9	c.61-1530G>C		intron_variant	Intron 1 of 4	1	NM_002998.4	ENSP00000307046.4

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28633 AN: 151968 Hom.: 3247 Cov.: 32

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.188 AC: 28635 AN: 152086 Hom.: 3246 Cov.: 32 AF XY: 0.195 AC XY: 14477 AN XY: 74318

African (AFR) AF: 0.0629 AC: 2611 AN: 41520

American (AMR) AF: 0.165 AC: 2523 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1759 AN: 5154

South Asian (SAS) AF: 0.355 AC: 1711 AN: 4816

European-Finnish (FIN) AF: 0.287 AC: 3024 AN: 10550

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15628 AN: 67986

Other (OTH) AF: 0.176 AC: 373 AN: 2116

Alfa AF: 0.210 Hom.: 449

Bravo AF: 0.169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.66
PhyloP100		0.59
Mutation Taster		=100/0	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: rs2028086; hg19: chr8-97604178;