8-96529915-C-T

Variant names:

• chr8-96529915-C-T
• rs874643
• NM_002998.4:c.60+35584C>T

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+35584C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 151,940 control chromosomes in the GnomAD database, including 49,221 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 0.80 (49221 hom., cov: 31)
• Consequence: SDC2 NM_002998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC2	NM_002998.4	c.60+35584C>T		intron_variant	Intron 1 of 4	ENST00000302190.9	NP_002989.2
SDC2	XM_047422076.1	c.-7538C>T		5_prime_UTR_variant	Exon 1 of 5		XP_047278032.1
SDC2	XM_024447228.2	c.-154+644C>T		intron_variant	Intron 1 of 5		XP_024302996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC2	ENST00000302190.9	c.60+35584C>T		intron_variant	Intron 1 of 4	1	NM_002998.4	ENSP00000307046.4

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120905 AN: 151822 Hom.: 49170 Cov.: 31

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.796 AC: 121009 AN: 151940 Hom.: 49221 Cov.: 31 AF XY: 0.785 AC XY: 58298 AN XY: 74248

African (AFR) AF: 0.896 AC: 37167 AN: 41474

American (AMR) AF: 0.662 AC: 10091 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2847 AN: 3466

East Asian (EAS) AF: 0.422 AC: 2165 AN: 5132

South Asian (SAS) AF: 0.620 AC: 2978 AN: 4806

European-Finnish (FIN) AF: 0.756 AC: 7973 AN: 10544

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55113 AN: 67952

Other (OTH) AF: 0.801 AC: 1687 AN: 2106

Alfa AF: 0.803 Hom.: 200358

Bravo AF: 0.798

Asia WGS AF: 0.561 AC: 1954 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	1.0
DANN	Benign	0.37
PhyloP100		-0.11
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: rs874643; hg19: chr8-97542143;