chr2-20202619-C-G

Position:

• chr2-20202619-C-G

Variant summary

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

The NM_002997.5(SDC1):​c.*147G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 773,762 control chromosomes in the GnomAD database, including 74,640 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 0.40 (12632 hom., cov: 31)
  • Exomes 𝑓: 0.44 (62008 hom.)
• Consequence: SDC1 NM_002997.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

Genes affected

SDC1 (HGNC:10658): (syndecan 1) 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-1 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-1 expression has been detected in several different tumor types. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC1	NM_002997.5	c.*147G>C		3_prime_UTR_variant	5/5	ENST00000254351.9	NP_002988.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC1	ENST00000254351	c.*147G>C		3_prime_UTR_variant	5/5	1	NM_002997.5	ENSP00000254351.4
SDC1	ENST00000403076.5	c.479-318G>C		intron_variant		1		ENSP00000384613.1
SDC1	ENST00000381150	c.*147G>C		3_prime_UTR_variant	6/6	5		ENSP00000370542.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60268 AN: 151902 Hom.: 12616 Cov.: 31

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.443 AC: 275546 AN: 621740 Hom.: 62008 Cov.: 8 AF XY: 0.442 AC XY: 143845 AN XY: 325178

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.433

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.397 AC: 60314 AN: 152022 Hom.: 12632 Cov.: 31 AF XY: 0.404 AC XY: 30040 AN XY: 74298

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.379

Alfa AF: 0.302 Hom.: 898

Bravo AF: 0.380

Asia WGS AF: 0.404 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.3
DANN	Benign	0.88

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: rs1131351; hg19: chr2-20402380; COSMIC: COSV54342223; COSMIC: COSV54342223;