Variant chr2-70181459-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017880.3(C2orf42):c.527C>T(p.Pro176Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000805 in 1,613,944 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 1 hom. )

Consequence

C2orf42
NM_017880.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 9.19

Variant links:

Genes affected

C2orf42 (HGNC:26056): (chromosome 2 open reading frame 42) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C2orf42 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012652814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2orf42	NM_017880.3 linkuse as main transcript	c.527C>T	p.Pro176Leu	missense_variant	3/10	ENST00000264434.7	NP_060350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
C2orf42	ENST00000264434.7 linkuse as main transcript	c.527C>T	p.Pro176Leu	missense_variant	3/10	1	NM_017880.3	ENSP00000264434	P1
C2orf42	ENST00000420306.1 linkuse as main transcript	c.527C>T	p.Pro176Leu	missense_variant	1/8	2		ENSP00000404515	P1
C2orf42	ENST00000417865.5 linkuse as main transcript			downstream_gene_variant		3		ENSP00000407799
C2orf42	ENST00000447804.1 linkuse as main transcript			downstream_gene_variant		4		ENSP00000396751

Frequencies

GnomAD3 genomes

AF:

0.000874

AC:

133

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000945

AC:

237

AN:

250822

Hom.:

AF XY:

0.000981

AC XY:

133

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00316

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000798

AC:

1167

AN:

1461710

Hom.:

Cov.:

AF XY:

0.000837

AC XY:

609

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.00218

Gnomad4 NFE exome

AF:

0.000835

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000874

AC:

133

AN:

152234

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.000906

Hom.:

Bravo

AF:

0.000808

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000931

AC:

113

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00148

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Nov 06, 2015

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

.;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

D;D

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.17

Sift

Benign

0.049

D;D

Sift4G

Benign

0.24

T;T

Polyphen

0.56

P;P

Vest4

0.35

MVP

0.37

MPC

0.42

ClinPred

0.044

GERP RS

5.0

Varity_R

0.13

gMVP

0.37

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