15-75675720-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001897.5(CSPG4):c.6799G>C(p.Gly2267Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSPG4 NM_001897.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40960854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSPG4	NM_001897.5	c.6799G>C	p.Gly2267Arg	missense_variant	10/10	ENST00000308508.5
CSPG4	XM_047432196.1	c.5737G>C	p.Gly1913Arg	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSPG4	ENST00000308508.5	c.6799G>C	p.Gly2267Arg	missense_variant	10/10	1	NM_001897.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

May 05, 2022

The c.6799G>C (p.G2267R) alteration is located in exon 10 (coding exon 10) of the CSPG4 gene. This alteration results from a G to C substitution at nucleotide position 6799, causing the glycine (G) at amino acid position 2267 to be replaced by an arginine (R). 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	0.36
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.27
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.53		Gain of MoRF binding (P = 0.0284);
MVP		0.51
MPC		1.2
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.16
gMVP		0.82

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: chr15-75968061;