chr2-20204251-GG-AA

Variant names:

• chr2-20204251-GG-AA
• NM_002997.5:c.188_189delCCinsTT
• SDC1 p.Ser63Phe

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002997.5(SDC1):​c.188_189delCCinsTT​(p.Ser63Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: SDC1 NM_002997.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002997.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC1	NM_002997.5	MANE Select	c.188_189delCCinsTT	p.Ser63Phe	missense	N/A	NP_002988.4
	SDC1	NM_001006946.2		c.188_189delCCinsTT	p.Ser63Phe	missense	N/A	NP_001006947.2	P18827

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC1	ENST00000254351.9	TSL:1 MANE Select	c.188_189delCCinsTT	p.Ser63Phe	missense	N/A	ENSP00000254351.4	P18827
	SDC1	ENST00000403076.5	TSL:1	c.188_189delCCinsTT	p.Ser63Phe	missense	N/A	ENSP00000384613.1	E9PHH3
	SDC1	ENST00000381150.5	TSL:5	c.188_189delCCinsTT	p.Ser63Phe	missense	N/A	ENSP00000370542.1	P18827

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-20404012;