dbSNP rs762292786: C2orf81:p.Gly411Arg (chr2-74414946-C-G) – ACMG Classification: Likely_benign (-2 pts)

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 𝑓: 7.2e-7 ( 0 hom. )

Consequence

C2orf81
NM_001316764.3 missense

Scores

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]

C2orf81 links:

ENSG00000159239 (HGNC:):

ENSG00000159239 links:

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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
C2orf81	NM_001316764.3 link	c.1231G>C	p.Gly411Arg	missense_variant	Exon 3 of 3	ENST00000684111.1	NP_001303693.1	A0A804HJ35
C2orf81	NM_001145054.2 link	c.1150G>C	p.Gly384Arg	missense_variant	Exon 4 of 4		NP_001138526.1	G3XAA6
C2orf81	NM_001316765.2 link	c.1084G>C	p.Gly362Arg	missense_variant	Exon 3 of 3		NP_001303694.1
C2orf81	NM_001316766.2 link	c.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
C2orf81	ENST00000684111.1 link	c.1231G>C	p.Gly411Arg	missense_variant	Exon 3 of 3		NM_001316764.3	ENSP00000507340.1		A0A804HJ35
ENSG00000159239	ENST00000517883.2 link	n.946G>C		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000431103.2		E5RJQ4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000679

AC:

AN:

147232

Hom.:

AF XY:

0.0000127

AC XY:

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:

AN:

1394018

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

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.:

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

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

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-1.1

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over