Variant chr2-74475026-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001365575.2(CCDC142):c.1886G>A(p.Arg629His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

CCDC142
NM_001365575.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Variant links:

Genes affected

CCDC142 (HGNC:25889): (coiled-coil domain containing 142)

CCDC142 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/exons	MANE	UniProt
CCDC142	NM_001365575.2 linkuse as main transcript	c.1886G>A	p.Arg629His	missense_variant	8/9	ENST00000393965.8
CCDC142	NM_032779.4 linkuse as main transcript	c.1865G>A	p.Arg622His	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC142	ENST00000393965.8 linkuse as main transcript	c.1886G>A	p.Arg629His	missense_variant	8/9	1	NM_001365575.2	P2	Q17RM4-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251232

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

0.0000636

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000800

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.1865G>A (p.R622H) alteration is located in exon 8 (coding exon 8) of the CCDC142 gene. This alteration results from a G to A substitution at nucleotide position 1865, causing the arginine (R) at amino acid position 622 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

T;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

0.50

N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.077

Sift

Benign

0.051

T;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.93

P;P

Vest4

0.66

MutPred

0.35

Gain of catalytic residue at L628 (P = 0.1302);.;

MVP

0.70

MPC

0.91

ClinPred

0.94

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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