Variant chr5-37153973-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_001384732.1(CPLANE1):c.8140C>T(p.Arg2714Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000247 in 1,458,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CPLANE1
NM_001384732.1 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:4U:1

Conservation

PhyloP100: 3.75

Variant links:

Genes affected

CPLANE1 (HGNC:25801): (ciliogenesis and planar polarity effector complex subunit 1) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. Defects in this gene are a cause of Joubert syndrome (JBTS). [provided by RefSeq, May 2012]

CPLANE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 18 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-37153973-G-A is Pathogenic according to our data. Variant chr5-37153973-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 217566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37153973-G-A is described in Lovd as [Pathogenic]. Variant chr5-37153973-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLANE1	NM_001384732.1 linkuse as main transcript	c.8140C>T	p.Arg2714Ter	stop_gained	42/53	ENST00000651892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLANE1	ENST00000651892.2 linkuse as main transcript	c.8140C>T	p.Arg2714Ter	stop_gained	42/53		NM_001384732.1	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249488

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1458048

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

724700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000119

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:4Uncertain:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome 17

Pathogenic:2Uncertain:1

Pathogenic, no assertion criteria provided	clinical testing	Dr.Nikuei Genetic Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Neurology Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University	-	- -
Pathogenic, criteria provided, single submitter	research	UW Hindbrain Malformation Research Program, University of Washington	Feb 23, 2015	- -

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 27, 2023

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 217566). This variant is also known as C5ORF42 p.R2660X. This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 22693042, 26092869, 33176815). This variant is present in population databases (rs147416429, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg2660*) in the CPLANE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPLANE1 are known to be pathogenic (PMID: 24178751, 26092869). -

Orofaciodigital syndrome type 6

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Nov 18, 2019

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Uncertain

0.37

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.38

MutationTaster

Benign

1.0

A;A;A

Vest4

0.12

GERP RS

5.2

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