Variant chr2-74474752-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001365575.2(CCDC142):c.2047A>C(p.Ser683Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCDC142
NM_001365575.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

Variant links:

Genes affected

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

CCDC142 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32933277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC142	NM_001365575.2 linkuse as main transcript	c.2047A>C	p.Ser683Arg	missense_variant	9/9	ENST00000393965.8
CCDC142	NM_032779.4 linkuse as main transcript	c.2026A>C	p.Ser676Arg	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC142	ENST00000393965.8 linkuse as main transcript	c.2047A>C	p.Ser683Arg	missense_variant	9/9	1	NM_001365575.2	P2	Q17RM4-1
CCDC142	ENST00000290418.4 linkuse as main transcript	c.2026A>C	p.Ser676Arg	missense_variant	9/9	2		A2	Q17RM4-2
CCDC142	ENST00000473278.1 linkuse as main transcript	n.617A>C		non_coding_transcript_exon_variant	3/3	2
CCDC142	ENST00000454193.5 linkuse as main transcript	c.1701+164A>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250964

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461450

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 10, 2024

The c.2026A>C (p.S676R) alteration is located in exon 9 (coding exon 9) of the CCDC142 gene. This alteration results from a A to C substitution at nucleotide position 2026, causing the serine (S) at amino acid position 676 to be replaced by an arginine (R). 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

Pathogenic

0.64

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

0.59

D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.95

P;P

Vest4

0.42

MutPred

0.17

Loss of phosphorylation at S683 (P = 0.0452);.;

MVP

0.77

MPC

0.50

ClinPred

0.81

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.38

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