Variant 2-208180784-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099334.3(C2orf80):c.327T>G(p.Ile109Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000275 in 1,613,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

C2orf80
NM_001099334.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.734

Variant links:

Genes affected

C2orf80 (HGNC:34352): (chromosome 2 open reading frame 80)

C2orf80 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0697667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2orf80	NM_001099334.3 linkuse as main transcript	c.327T>G	p.Ile109Met	missense_variant	6/9	ENST00000341287.9	NP_001092804.2	Q0P641

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2orf80	ENST00000341287.9 linkuse as main transcript	c.327T>G	p.Ile109Met	missense_variant	6/9	1	NM_001099334.3	ENSP00000343171.4		Q0P641

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000200

AC:

AN:

249414

Hom.:

AF XY:

0.000207

AC XY:

AN XY:

135312

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000696

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000283

AC:

414

AN:

1461472

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

197

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000862

Gnomad4 NFE exome

AF:

0.000301

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000191

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000282

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000245

AC:

ExAC

AF:

0.000199

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

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

Sep 17, 2021

The c.327T>G (p.I109M) alteration is located in exon 6 (coding exon 5) of the C2orf80 gene. This alteration results from a T to G substitution at nucleotide position 327, causing the isoleucine (I) at amino acid position 109 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.035

.;T;.;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.68

T;T;T;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.070

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L;.;.;.

MutationTaster

Benign

0.99

N;N;N

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.044

D;T;D;T;T

Sift4G

Benign

0.061

T;T;T;T;.

Polyphen

0.19

.;B;.;.;.

Vest4

0.36, 0.36, 0.32

MVP

0.23

MPC

0.042

ClinPred

0.037

GERP RS

-0.74

Varity_R

0.13

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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