rs529632713

Variant names:

• chr15-75676004-C-A
• rs529632713
• NM_001897.5:c.6515G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-75676004-C-A
• chr15-75676004-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001897.5(CSPG4):​c.6515G>T​(p.Ser2172Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,418,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. S2172N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CSPG4 NM_001897.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

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]

CSPG4 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000260892 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10024738).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001897.5. 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
	CSPG4	NM_001897.5	MANE Select	c.6515G>T	p.Ser2172Ile	missense	Exon 10 of 10	NP_001888.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPG4	ENST00000308508.5	TSL:1 MANE Select	c.6515G>T	p.Ser2172Ile	missense	Exon 10 of 10	ENSP00000312506.5	Q6UVK1
	CSPG4	ENST00000941445.1		c.3794G>T	p.Ser1265Ile	missense	Exon 10 of 10	ENSP00000611504.1
	CSPG4	ENST00000900311.1		c.2978G>T	p.Ser993Ile	missense	Exon 9 of 9	ENSP00000570370.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1418402 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 702272

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32918

American (AMR) AF: 0.00 AC: 0 AN: 42276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24460

East Asian (EAS) AF: 0.00 AC: 0 AN: 39062

South Asian (SAS) AF: 0.00 AC: 0 AN: 82084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1095346

Other (OTH) AF: 0.00 AC: 0 AN: 58894

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000812204), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.054
Sift	Benign	0.16	T
Sift4G	Uncertain	0.013	D
Polyphen		0.34	B
Vest4		0.14
MutPred		0.37		Loss of disorder (P = 0.0071)
MVP		0.29
MPC		0.53
ClinPred		0.49	T
GERP RS		4.3
Varity_R		0.14
gMVP		0.67
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs529632713; hg19: chr15-75968345;