dbSNP rs141168630: CPLANE2:p.Arg111Cys (chr1-16232952-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_030907.4(CPLANE2):c.331C>T(p.Arg111Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CPLANE2
NM_030907.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

Variant links:

Genes affected

CPLANE2 (HGNC:28127): (ciliogenesis and planar polarity effector complex subunit 2) Predicted to enable GTP binding activity and GTPase activity. Predicted to be involved in cellular protein localization; cilium assembly; and regulation of vesicle-mediated transport. Predicted to be located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

CPLANE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
CPLANE2	NM_030907.4 link	c.331C>T	p.Arg111Cys	missense_variant	Exon 3 of 5	ENST00000375599.8	NP_112169.2	Q9BU20
CPLANE2	XM_011542126.4 link	c.331C>T	p.Arg111Cys	missense_variant	Exon 3 of 5		XP_011540428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLANE2	ENST00000375599.8 link	c.331C>T	p.Arg111Cys	missense_variant	Exon 3 of 5	1	NM_030907.4	ENSP00000364749.2		Q9BU20
CPLANE2	ENST00000434014.1 link	c.181-306C>T		intron_variant	Intron 2 of 3	5		ENSP00000406390.1		H0Y6L8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251462

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.331C>T (p.R111C) alteration is located in exon 3 (coding exon 3) of the RSG1 gene. This alteration results from a C to T substitution at nucleotide position 331, causing the arginine (R) at amino acid position 111 to be replaced by a cysteine (C). 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

Benign

0.12

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

Eigen

Benign

-0.068

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.71

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.45

Sift

Benign

0.048

Sift4G

Benign

0.097

Polyphen

0.17

Vest4

0.51

MVP

0.72

MPC

0.38

ClinPred

0.78

GERP RS

4.8

Varity_R

0.26

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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