Genetic Variant C2orf81:p.Ala49Thr (chr2-74416115-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001316764.3(C2orf81):c.145G>A(p.Ala49Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,536,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

C2orf81
NM_001316764.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0370

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.13326466).

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.145G>A	p.Ala49Thr	missense	Exon 2 of 3	NP_001303693.1	A0A804HJ35
C2orf81	NM_001145054.2		c.154G>A	p.Ala52Thr	missense	Exon 2 of 4	NP_001138526.1	G3XAA6
C2orf81	NM_001316766.2		c.-224G>A		5_prime_UTR	Exon 2 of 2	NP_001303695.1	A0A1W2PQG2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2orf81	ENST00000684111.1	MANE Select	c.145G>A	p.Ala49Thr	missense	Exon 2 of 3	ENSP00000507340.1	A0A804HJ35
ENSG00000159239	ENST00000517883.2	TSL:5	n.-224G>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000431103.2	E5RJQ4
ENSG00000159239	ENST00000517883.2	TSL:5	n.-224G>A		5_prime_UTR	Exon 2 of 5	ENSP00000431103.2	E5RJQ4

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000205

AC:

AN:

155780

AF XY:

0.000218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000614

Gnomad NFE exome

AF:

0.000480

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.000430

AC:

595

AN:

1384118

Hom.:

Cov.:

AF XY:

0.000378

AC XY:

258

AN XY:

682432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31364

American (AMR)

AF:

0.00

AC:

AN:

35168

Ashkenazi Jewish (ASJ)

AF:

0.0000402

AC:

AN:

24846

East Asian (EAS)

AF:

0.00

AC:

AN:

34654

South Asian (SAS)

AF:

0.00

AC:

AN:

78262

European-Finnish (FIN)

AF:

0.0000636

AC:

AN:

47134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.000538

AC:

576

AN:

1069920

Other (OTH)

AF:

0.000263

AC:

AN:

57138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

101

134

168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000210

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000964

AC:

AN:

41474

American (AMR)

AF:

0.000196

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68040

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000360

Hom.:

Bravo

AF:

0.000204

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000156

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

0.21

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.94

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.67

M_CAP

Benign

0.0054

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.93

PhyloP100

0.037

PROVEAN

Benign

-1.8

REVEL

Benign

0.11

Sift

Uncertain

0.017

Sift4G

Uncertain

0.036

Polyphen

0.99

Vest4

0.24

MVP

0.072

ClinPred

0.16

GERP RS

4.6

PromoterAI

0.13

Neutral

(source)

Varity_R

0.064

Mutation Taster

=93/7

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