NM_002998.4:c.175G>C

Variant names:

• chr8-96602397-G-C
• NM_002998.4:c.175G>C

Variant summary

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

The NM_002998.4(SDC2):​c.175G>C​(p.Ala59Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A59T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SDC2 NM_002998.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36

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 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 rank	MANE	Protein	UniProt
SDC2	NM_002998.4	c.175G>C	p.Ala59Pro	missense_variant, splice_region_variant	Exon 3 of 5	ENST00000302190.9	NP_002989.2
SDC2	XM_011517212.4	c.88G>C	p.Ala30Pro	missense_variant, splice_region_variant	Exon 4 of 6		XP_011515514.1
SDC2	XM_024447228.2	c.88G>C	p.Ala30Pro	missense_variant, splice_region_variant	Exon 4 of 6		XP_024302996.1
SDC2	XM_047422076.1	c.88G>C	p.Ala30Pro	missense_variant, splice_region_variant	Exon 3 of 5		XP_047278032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC2	ENST00000302190.9	c.175G>C	p.Ala59Pro	missense_variant, splice_region_variant	Exon 3 of 5	1	NM_002998.4	ENSP00000307046.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461306 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726918

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.;.;.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;T;.;T;D;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.63	D;D;D;D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.6	M;.;.;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.010	N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.14	T;D;T;T;T;T
Sift4G	Benign	0.25	T;T;T;T;T;T
Polyphen		0.95	P;.;.;.;.;.
Vest4		0.34
MutPred		0.49		Loss of stability (P = 0.0828);.;.;.;.;.;
MVP		0.47
MPC		0.89
ClinPred		0.77	D
GERP RS		4.2
Varity_R		0.073
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-97614625;