dbSNP rs747454015: C2orf81:p.Gly323Glu (chr2-74415209-C-T) – 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.968G>A(p.Gly323Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000433 in 1,548,656 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 1 hom. )

Consequence

C2orf81
NM_001316764.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.959

Publications

2 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:

Genome browser will be placed here

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=0.015669793).

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.968G>A	p.Gly323Glu	missense	Exon 3 of 3	NP_001303693.1	A0A804HJ35
C2orf81	NM_001145054.2		c.887G>A	p.Gly296Glu	missense	Exon 4 of 4	NP_001138526.1	G3XAA6
C2orf81	NM_001316765.2		c.821G>A	p.Gly274Glu	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.968G>A	p.Gly323Glu	missense	Exon 3 of 3	ENSP00000507340.1	A0A804HJ35
ENSG00000159239	ENST00000517883.2	TSL:5	n.683G>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000431103.2	E5RJQ4
C2orf81	ENST00000290390.9	TSL:5	c.887G>A	p.Gly296Glu	missense	Exon 4 of 4	ENSP00000290390.5	G3XAA6

Frequencies

GnomAD3 genomes

AF:

0.0000465

AC:

AN:

150562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000916

AC:

AN:

152758

AF XY:

0.000123

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000952

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000429

AC:

AN:

1398094

Hom.:

Cov.:

AF XY:

0.0000450

AC XY:

AN XY:

689552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31562

American (AMR)

AF:

0.0000281

AC:

AN:

35630

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

25130

East Asian (EAS)

AF:

0.00

AC:

AN:

35692

South Asian (SAS)

AF:

0.00

AC:

AN:

79168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48590

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0000176

AC:

AN:

1078662

Other (OTH)

AF:

0.000155

AC:

AN:

57968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000465

AC:

AN:

150562

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40146

American (AMR)

AF:

0.00

AC:

AN:

15156

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5014

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000406

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.1

(source)

DANN

Benign

0.67

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.45

M_CAP

Benign

0.013

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

PhyloP100

-0.96

PROVEAN

Benign

-0.53

REVEL

Benign

0.039

Sift

Benign

0.61

Sift4G

Benign

1.0

Polyphen

0.015

Vest4

0.050

MutPred

0.33

Gain of solvent accessibility (P = 0.0456)

MVP

0.067

ClinPred

0.011

GERP RS

-0.96

Varity_R

0.056

gMVP

0.050

Mutation Taster

=99/1

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over