rs2440681

Positions:

• chr8-96532353-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002998.4(SDC2):​c.60+38022G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 147,572 control chromosomes in the GnomAD database, including 8,442 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 0.33 (8442 hom., cov: 26)
• Consequence: SDC2 NM_002998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC2	NM_002998.4	c.60+38022G>A		intron_variant		ENST00000302190.9	NP_002989.2
SDC2	XM_047422076.1	c.-5100G>A		5_prime_UTR_variant	1/5		XP_047278032.1
SDC2	XM_024447228.2	c.-154+3082G>A		intron_variant			XP_024302996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC2	ENST00000302190.9	c.60+38022G>A		intron_variant		1	NM_002998.4	ENSP00000307046	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 49357 AN: 147486 Hom.: 8424 Cov.: 26

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.461

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.335 AC: 49413 AN: 147572 Hom.: 8442 Cov.: 26 AF XY: 0.335 AC XY: 23975 AN XY: 71668

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.325

Alfa AF: 0.351 Hom.: 18209

Bravo AF: 0.329

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.51

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: rs2440681; hg19: chr8-97544581;