Genetic Variant NM_001316764.3:c.1231G>C (chr2-74414946-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 14/18 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

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04938343).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316764.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2orf81	NM_001316764.3	MANE Select	c.1231G>C	p.Gly411Arg	missense	Exon 3 of 3	NP_001303693.1	A0A804HJ35
C2orf81	NM_001145054.2		c.1150G>C	p.Gly384Arg	missense	Exon 4 of 4	NP_001138526.1	G3XAA6
C2orf81	NM_001316765.2		c.1084G>C	p.Gly362Arg	missense	Exon 3 of 3	NP_001303694.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2orf81	ENST00000684111.1	MANE Select	c.1231G>C	p.Gly411Arg	missense	Exon 3 of 3	ENSP00000507340.1	A0A804HJ35
ENSG00000159239	ENST00000517883.2	TSL:5	n.946G>C		non_coding_transcript_exon	Exon 2 of 5	ENSP00000431103.2	E5RJQ4
C2orf81	ENST00000290390.9	TSL:5	c.1150G>C	p.Gly384Arg	missense	Exon 4 of 4	ENSP00000290390.5	G3XAA6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000679

AC:

AN:

147232

AF XY:

0.0000127

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 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

African (AFR)

AF:

0.00

AC:

AN:

31494

American (AMR)

AF:

0.00

AC:

AN:

35474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25008

East Asian (EAS)

AF:

0.00

AC:

AN:

35660

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076422

Other (OTH)

AF:

0.00

AC:

AN:

57742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.31

(source)

DANN

Benign

0.49

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.57

M_CAP

Benign

0.0086

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.1

PhyloP100

-2.7

PROVEAN

Benign

-0.72

REVEL

Benign

0.015

Sift

Benign

0.33

Sift4G

Benign

0.13

Polyphen

0.0090

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

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over