rs2253255

Variant names:

• chr8-96510315-A-G
• rs2253255
• NM_002998.4:c.60+15984A>G

Variant summary

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

The NM_002998.4(SDC2):​c.60+15984A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 152,186 control chromosomes in the GnomAD database, including 849 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 0.083 (849 hom., cov: 32)
• Consequence: SDC2 NM_002998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC2	NM_002998.4	c.60+15984A>G		intron_variant	Intron 1 of 4	ENST00000302190.9	NP_002989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC2	ENST00000302190.9	c.60+15984A>G		intron_variant	Intron 1 of 4	1	NM_002998.4	ENSP00000307046.4

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12649 AN: 152068 Hom.: 845 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0386

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0834 AC: 12690 AN: 152186 Hom.: 849 Cov.: 32 AF XY: 0.0835 AC XY: 6216 AN XY: 74420

African (AFR) AF: 0.181 AC: 7504 AN: 41510

American (AMR) AF: 0.0345 AC: 527 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3472

East Asian (EAS) AF: 0.169 AC: 872 AN: 5170

South Asian (SAS) AF: 0.117 AC: 562 AN: 4820

European-Finnish (FIN) AF: 0.0336 AC: 356 AN: 10610

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0386 AC: 2626 AN: 67998

Other (OTH) AF: 0.0714 AC: 151 AN: 2114

Alfa AF: 0.0527 Hom.: 1387

Bravo AF: 0.0874

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.37
PhyloP100		0.15
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: rs2253255; hg19: chr8-97522543;