Variant 2-199925738-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153689.6(C2orf69):c.1010G>A(p.Arg337His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,890 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 4 hom. )

Consequence

C2orf69
NM_153689.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.708

Variant links:

Genes affected

C2orf69 (HGNC:26799): (chromosome 2 open reading frame 69) Involved in oxidative phosphorylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

C2orf69 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017250538).

BP6

Variant 2-199925738-G-A is Benign according to our data. Variant chr2-199925738-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1879515.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C2orf69	NM_153689.6 linkuse as main transcript	c.1010G>A	p.Arg337His	missense_variant	2/2	ENST00000319974.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2orf69	ENST00000319974.6 linkuse as main transcript	c.1010G>A	p.Arg337His	missense_variant	2/2	1	NM_153689.6	P1
C2orf69	ENST00000491721.1 linkuse as main transcript	n.466+13967G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000546

AC:

136

AN:

249076

Hom.:

AF XY:

0.000688

AC XY:

AN XY:

135124

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00386

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000283

AC:

413

AN:

1461596

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

303

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00399

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000184

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000493

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00106

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000629

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

C2orf69: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.73

M_CAP

Benign

0.0016

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.82

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Benign

0.56

Sift4G

Benign

0.48

Polyphen

0.0040

Vest4

0.036

MVP

0.055

MPC

0.41

ClinPred

0.0083

GERP RS

-1.6

Varity_R

0.017

gMVP

0.25

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