15-75675593-C-A

Variant names:

• chr15-75675593-C-A
• rs186191601
• NM_001897.5:c.6926G>T

Variant summary

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

The NM_001897.5(CSPG4):​c.6926G>T​(p.Arg2309Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000441 in 1,360,124 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: CSPG4 NM_001897.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93

Genes affected

CSPG4 (HGNC:2466): (chondroitin sulfate proteoglycan 4) A human melanoma-associated chondroitin sulfate proteoglycan plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. CSPG4 represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells. [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
CSPG4	NM_001897.5	c.6926G>T	p.Arg2309Leu	missense_variant	Exon 10 of 10	ENST00000308508.5	NP_001888.2
CSPG4	XM_047432196.1	c.5864G>T	p.Arg1955Leu	missense_variant	Exon 10 of 10		XP_047288152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSPG4	ENST00000308508.5	c.6926G>T	p.Arg2309Leu	missense_variant	Exon 10 of 10	1	NM_001897.5	ENSP00000312506.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000115 AC: 2 AN: 173664 Hom.: 0 AF XY: 0.0000218 AC XY: 2 AN XY: 91588

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000237

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000441 AC: 6 AN: 1360124 Hom.: 0 Cov.: 32 AF XY: 0.00000451 AC XY: 3 AN XY: 665576

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: 0.00000565

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000172 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.58
MutPred		0.46		Loss of MoRF binding (P = 0.0632);
MVP		0.39
MPC		1.2
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.23
gMVP		0.71

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: rs186191601; hg19: chr15-75967934;