rs777304384

Variant names:

• chr2-20204252-G-A
• rs777304384
• NM_002997.5:c.188C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_002997.5(SDC1):​c.188C>T​(p.Ser63Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,446,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SDC1 NM_002997.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.17
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14245251).
• BP6: Variant 2-20204252-G-A is Benign according to our data. Variant chr2-20204252-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 207901.Status of the report is no_assertion_criteria_provided, 0 stars.

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.188C>T	p.Ser63Phe	missense	Exon 3 of 5	NP_002988.4
	SDC1	NM_001006946.2		c.188C>T	p.Ser63Phe	missense	Exon 4 of 6	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.188C>T	p.Ser63Phe	missense	Exon 3 of 5	ENSP00000254351.4	P18827
	SDC1	ENST00000403076.5	TSL:1	c.188C>T	p.Ser63Phe	missense	Exon 3 of 4	ENSP00000384613.1	E9PHH3
	SDC1	ENST00000381150.5	TSL:5	c.188C>T	p.Ser63Phe	missense	Exon 4 of 6	ENSP00000370542.1	P18827

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000421 AC: 1 AN: 237666 AF XY: 0.00000772

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1446576 Hom.: 0 Cov.: 38 AF XY: 0.00000417 AC XY: 3 AN XY: 720022

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111784

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 29

ExAC AF: 0.00000825 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.2
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.019
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.025	D
Polyphen		0.046	B
Vest4		0.18
MutPred		0.43		Loss of glycosylation at S63 (P = 0.0244)
MVP		0.31
MPC		0.28
ClinPred		0.13	T
GERP RS		2.4
Varity_R		0.061
gMVP		0.13
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs777304384; hg19: chr2-20404013;