8-96522423-C-T

Position:

• chr8-96522423-C-T

Variant summary

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

The NM_002998.4(SDC2):​c.60+28092C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,756 control chromosomes in the GnomAD database, including 29,996 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 0.62 (29996 hom., cov: 31)
• Consequence: SDC2 NM_002998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC2	NM_002998.4	c.60+28092C>T		intron_variant		ENST00000302190.9
SDC2	XM_024447228.2	c.-7002C>T		5_prime_UTR_variant	1/6
SDC2	XM_047422076.1	c.-15030C>T		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC2	ENST00000302190.9	c.60+28092C>T		intron_variant		1	NM_002998.4	P1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 93817 AN: 151638 Hom.: 29987 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.618 AC: 93859 AN: 151756 Hom.: 29996 Cov.: 31 AF XY: 0.606 AC XY: 44900 AN XY: 74148

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.632

Alfa AF: 0.653 Hom.: 45509

Bravo AF: 0.611

Asia WGS AF: 0.366 AC: 1274 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.53

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: rs2575735; hg19: chr8-97534651;