rs762292786

Variant summary

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

The NM_001316764.3(C2orf81):​c.1231G>C​(p.Gly411Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G411S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

C2orf81
NM_001316764.3 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.71
Variant links:
Genes affected
C2orf81 (HGNC:34350): (chromosome 2 open reading frame 81) Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.04938343).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C2orf81NM_001316764.3 linkc.1231G>C p.Gly411Arg missense_variant Exon 3 of 3 ENST00000684111.1 NP_001303693.1 A0A804HJ35
C2orf81NM_001145054.2 linkc.1150G>C p.Gly384Arg missense_variant Exon 4 of 4 NP_001138526.1 G3XAA6
C2orf81NM_001316765.2 linkc.1084G>C p.Gly362Arg missense_variant Exon 3 of 3 NP_001303694.1
C2orf81NM_001316766.2 linkc.946G>C p.Gly316Arg missense_variant Exon 2 of 2 NP_001303695.1 A0A1W2PQG2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C2orf81ENST00000684111.1 linkc.1231G>C p.Gly411Arg missense_variant Exon 3 of 3 NM_001316764.3 ENSP00000507340.1 A0A804HJ35
ENSG00000159239ENST00000517883.2 linkn.946G>C non_coding_transcript_exon_variant Exon 2 of 5 5 ENSP00000431103.2 E5RJQ4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000679
AC:
1
AN:
147232
Hom.:
0
AF XY:
0.0000127
AC XY:
1
AN XY:
78768
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:
0.0000445
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.17e-7
AC:
1
AN:
1394018
Hom.:
0
Cov.:
32
AF XY:
0.00000146
AC XY:
1
AN XY:
687130
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:
0.0000127
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.31
DANN
Benign
0.49
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.57
T;T;T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.049
T;T;T
MetaSVM
Benign
-1.1
T
PROVEAN
Benign
-0.72
.;.;N
REVEL
Benign
0.015
Sift
Benign
0.33
.;.;T
Sift4G
Benign
0.13
T;.;T
Polyphen
0.0090
.;.;B
Vest4
0.060
MutPred
0.14
.;.;Loss of methylation at R383 (P = 0.0467);
MVP
0.17
ClinPred
0.044
T
GERP RS
-3.7
Varity_R
0.091
gMVP
0.087

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.

Other links and lift over

dbSNP: rs762292786; hg19: chr2-74642073; API