2-20224830-A-G

Position:

• chr2-20224830-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002997.5(SDC1):​c.38T>C​(p.Leu13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SDC1 NM_002997.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC1	NM_002997.5	c.38T>C	p.Leu13Pro	missense_variant	1/5	ENST00000254351.9	NP_002988.4
SDC1	NM_001006946.2	c.38T>C	p.Leu13Pro	missense_variant	2/6		NP_001006947.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC1	ENST00000254351.9	c.38T>C	p.Leu13Pro	missense_variant	1/5	1	NM_002997.5	ENSP00000254351.4
SDC1	ENST00000403076.5	c.38T>C	p.Leu13Pro	missense_variant	1/4	1		ENSP00000384613.1
SDC1	ENST00000381150.5	c.38T>C	p.Leu13Pro	missense_variant	2/6	5		ENSP00000370542.1
SDC1	ENST00000447124.1	n.38T>C		non_coding_transcript_exon_variant	1/4	4		ENSP00000390201.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1137350 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 549526

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.38T>C (p.L13P) alteration is located in exon 2 (coding exon 1) of the SDC1 gene. This alteration results from a T to C substitution at nucleotide position 38, causing the leucine (L) at amino acid position 13 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Uncertain	0.55	D;D;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.43	.;T;T
M_CAP	Pathogenic	0.77	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.30	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.49
MutPred		0.78		Loss of stability (P = 0.0057);Loss of stability (P = 0.0057);Loss of stability (P = 0.0057);
MVP		0.56
MPC		0.37
ClinPred		0.62	D
GERP RS		1.9
Varity_R		0.62
gMVP		0.41

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: rs1677939260; hg19: chr2-20424591;