Variant rs1554117456 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.247G>T(p.Gly83*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000728 in 1,373,372 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

CPLANE1
NM_001384732.1 stop_gained

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:3

Conservation

PhyloP100: 7.17

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 5-37245569-C-A is Pathogenic according to our data. Variant chr5-37245569-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 520682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPLANE1	NM_001384732.1 link	c.247G>T	p.Gly83*	stop_gained	4/53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CPLANE1	ENST00000651892.2 link	c.247G>T	p.Gly83*	stop_gained	4/53		NM_001384732.1	ENSP00000498265.2	A0A494BZW6
CPLANE1	ENST00000508244.5 link	c.247G>T	p.Gly83*	stop_gained	3/51	5		ENSP00000421690.1	Q9H799-1
CPLANE1	ENST00000425232.7 link	n.28G>T		non_coding_transcript_exon_variant	1/30	5		ENSP00000389014.3	A0A7I2XYG4
CPLANE1	ENST00000675547.1 link	n.550G>T		non_coding_transcript_exon_variant	2/15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000702

AC:

AN:

142460

Hom.:

AF XY:

0.00

AC XY:

AN XY:

75416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000101

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.28e-7

AC:

AN:

1373372

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676276

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000286

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Orofaciodigital syndrome type 6;C3553264:Joubert syndrome 17

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 26, 2024

- -

Inborn genetic diseases

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2015

Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected -

Joubert syndrome and related disorders

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Nov 29, 2022

Variant summary: CPLANE1 c.247G>T (p.Gly83X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 7e-06 in 142460 control chromosomes. To our knowledge, no occurrence of c.247G>T in individuals affected with Joubert Syndrome And Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, classifying the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.99

FATHMM_MKL

Pathogenic

0.99

Vest4

0.38

GERP RS

5.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.26

Position offset: 29

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

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