rs2575702

Variant names:

• chr8-96579620-T-C
• rs2575702
• NM_002998.4:c.61-13860T>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.61-13860T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,114 control chromosomes in the GnomAD database, including 28,118 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 0.59 (28118 hom., cov: 33)
• Consequence: SDC2 NM_002998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 4 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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC2	NM_002998.4	c.61-13860T>C		intron_variant	Intron 1 of 4	ENST00000302190.9	NP_002989.2
SDC2	XM_024447228.2	c.-27-13860T>C		intron_variant	Intron 2 of 5		XP_024302996.1
SDC2	XM_047422076.1	c.-27-13860T>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.61-13860T>C		intron_variant	Intron 1 of 4	1	NM_002998.4	ENSP00000307046.4
SDC2	ENST00000522911.5	c.-27-13860T>C		intron_variant	Intron 1 of 4	3		ENSP00000427784.1
SDC2	ENST00000518385.5	c.65-22775T>C		intron_variant	Intron 1 of 3	5		ENSP00000429045.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90437 AN: 151996 Hom.: 28116 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.595 AC: 90461 AN: 152114 Hom.: 28118 Cov.: 33 AF XY: 0.584 AC XY: 43441 AN XY: 74366

African (AFR) AF: 0.542 AC: 22499 AN: 41476

American (AMR) AF: 0.542 AC: 8284 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2265 AN: 3472

East Asian (EAS) AF: 0.126 AC: 651 AN: 5172

South Asian (SAS) AF: 0.418 AC: 2017 AN: 4824

European-Finnish (FIN) AF: 0.617 AC: 6525 AN: 10576

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46076 AN: 67998

Other (OTH) AF: 0.602 AC: 1271 AN: 2110

Alfa AF: 0.644 Hom.: 15946

Bravo AF: 0.591

Asia WGS AF: 0.302 AC: 1053 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.24
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: rs2575702; hg19: chr8-97591848;