Genetic Variant CSPG4:p.Thr2261Asn (chr15-75675737-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001897.5(CSPG4):c.6782C>A(p.Thr2261Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000252 in 1,603,696 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

CSPG4
NM_001897.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.33

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006762594).

BP6

Variant 15-75675737-G-T is Benign according to our data. Variant chr15-75675737-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 744383.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPG4	NM_001897.5 link	c.6782C>A	p.Thr2261Asn	missense_variant	Exon 10 of 10	ENST00000308508.5	NP_001888.2	Q6UVK1
CSPG4	XM_047432196.1 link	c.5720C>A	p.Thr1907Asn	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 link	c.6782C>A	p.Thr2261Asn	missense_variant	Exon 10 of 10	1	NM_001897.5	ENSP00000312506.5		Q6UVK1

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

186

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000326

AC:

AN:

245608

Hom.:

AF XY:

0.000234

AC XY:

AN XY:

132640

show subpopulations

Gnomad AFR exome

AF:

0.00475

Gnomad AMR exome

AF:

0.0000293

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:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000149

AC:

216

AN:

1451330

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

720618

show subpopulations

Gnomad4 AFR exome

AF:

0.00550

Gnomad4 AMR exome

AF:

0.0000452

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:

0.00000181

Gnomad4 OTH exome

AF:

0.000484

GnomAD4 genome

AF:

0.00123

AC:

188

AN:

152366

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00442

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000306

Hom.:

Bravo

AF:

0.00144

ESP6500AA

AF:

0.00501

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000404

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.093

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0068

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.67

REVEL

Benign

0.039

Sift

Benign

0.13

Sift4G

Benign

0.16

Polyphen

0.20

Vest4

0.11

MVP

0.26

MPC

0.62

ClinPred

0.048

GERP RS

5.0

Varity_R

0.15

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over