Variant chr2-178856319-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173648.4(CCDC141):c.2803C>T(p.Arg935Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 1,608,436 control chromosomes in the GnomAD database, including 5,410 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.060 ( 363 hom., cov: 32)

Exomes 𝑓: 0.078 ( 5047 hom. )

Consequence

CCDC141
NM_173648.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.20

Variant links:

Genes affected

CCDC141 (HGNC:26821): (coiled-coil domain containing 141) Predicted to be involved in axon guidance and cell adhesion. Predicted to act upstream of or within centrosome localization and cerebral cortex radially oriented cell migration. Predicted to be located in centrosome; cytoplasm; and plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

CCDC141 links:

ENSG00000287149 (HGNC:):

ENSG00000287149 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028259456).

BP6

Variant 2-178856319-G-A is Benign according to our data. Variant chr2-178856319-G-A is described in ClinVar as [Benign]. Clinvar id is 1231630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC141	NM_173648.4 linkuse as main transcript	c.2803C>T	p.Arg935Trp	missense_variant	18/24	ENST00000443758.7	NP_775919.3	Q6ZP82-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC141	ENST00000443758.7 linkuse as main transcript	c.2803C>T	p.Arg935Trp	missense_variant	18/24	5	NM_173648.4	ENSP00000390190.2		Q6ZP82-2

Frequencies

GnomAD3 genomes

AF:

0.0603

AC:

9155

AN:

151946

Hom.:

363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0656

Gnomad ASJ

AF:

0.0554

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0268

Gnomad FIN

AF:

0.0724

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0914

Gnomad OTH

AF:

0.0628

GnomAD3 exomes

AF:

0.0603

AC:

15016

AN:

248924

Hom.:

570

AF XY:

0.0607

AC XY:

8175

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.0490

Gnomad ASJ exome

AF:

0.0522

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.0275

Gnomad FIN exome

AF:

0.0725

Gnomad NFE exome

AF:

0.0867

Gnomad OTH exome

AF:

0.0725

GnomAD4 exome

AF:

0.0779

AC:

113436

AN:

1456372

Hom.:

5047

Cov.:

AF XY:

0.0768

AC XY:

55638

AN XY:

724436

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.0508

Gnomad4 ASJ exome

AF:

0.0518

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0292

Gnomad4 FIN exome

AF:

0.0730

Gnomad4 NFE exome

AF:

0.0887

Gnomad4 OTH exome

AF:

0.0722

GnomAD4 genome

AF:

0.0602

AC:

9152

AN:

152064

Hom.:

363

Cov.:

AF XY:

0.0596

AC XY:

4433

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0160

Gnomad4 AMR

AF:

0.0655

Gnomad4 ASJ

AF:

0.0554

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0270

Gnomad4 FIN

AF:

0.0724

Gnomad4 NFE

AF:

0.0915

Gnomad4 OTH

AF:

0.0621

Alfa

AF:

0.0818

Hom.:

1357

Bravo

AF:

0.0560

TwinsUK

AF:

0.0874

AC:

324

ALSPAC

AF:

0.0760

AC:

293

ESP6500AA

AF:

0.0234

AC:

103

ESP6500EA

AF:

0.0902

AC:

775

ExAC

AF:

0.0617

AC:

7490

Asia WGS

AF:

0.0110

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 29748316, 30012220) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Pathogenic

1.0

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-6.1

D;D

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

ClinPred

0.035

GERP RS

5.0

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