2-74416115-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 12/15 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

3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0370
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13326466).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C2orf81NM_001316764.3 linkc.145G>A p.Ala49Thr missense_variant Exon 2 of 3 ENST00000684111.1 NP_001303693.1 A0A804HJ35
C2orf81NM_001145054.2 linkc.154G>A p.Ala52Thr missense_variant Exon 2 of 4 NP_001138526.1 G3XAA6
C2orf81NM_001316766.2 linkc.-224G>A 5_prime_UTR_variant Exon 2 of 2 NP_001303695.1 A0A1W2PQG2
C2orf81NM_001316765.2 linkc.102+43G>A intron_variant Intron 2 of 2 NP_001303694.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C2orf81ENST00000684111.1 linkc.145G>A p.Ala49Thr missense_variant Exon 2 of 3 NM_001316764.3 ENSP00000507340.1 A0A804HJ35
ENSG00000159239ENST00000517883.2 linkn.-224G>A non_coding_transcript_exon_variant Exon 2 of 5 5 ENSP00000431103.2 E5RJQ4
ENSG00000159239ENST00000517883.2 linkn.-224G>A 5_prime_UTR_variant Exon 2 of 5 5 ENSP00000431103.2 E5RJQ4

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152256
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.000205
AC:
32
AN:
155780
Hom.:
0
AF XY:
0.000218
AC XY:
18
AN XY:
82656
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 SAS 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.:
0
Cov.:
32
AF XY:
0.000378
AC XY:
258
AN XY:
682432
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000402
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000636
Gnomad4 NFE exome
AF:
0.000538
Gnomad4 OTH exome
AF:
0.000263
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152256
Hom.:
0
Cov.:
32
AF XY:
0.000255
AC XY:
19
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0000964
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000360
Hom.:
0
Bravo
AF:
0.000204
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.000156
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 12, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.154G>A (p.A52T) alteration is located in exon 2 (coding exon 2) of the C2orf81 gene. This alteration results from a G to A substitution at nucleotide position 154, causing the alanine (A) at amino acid position 52 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
19
DANN
Benign
0.94
Eigen
Uncertain
0.23
Eigen_PC
Benign
0.15
FATHMM_MKL
Benign
0.071
N
LIST_S2
Benign
0.67
T;T;T;T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.13
T;T;T;T
MetaSVM
Benign
-0.93
T
PROVEAN
Benign
-1.8
.;N;.;.
REVEL
Benign
0.11
Sift
Uncertain
0.017
.;D;.;.
Sift4G
Uncertain
0.036
D;D;.;.
Polyphen
0.99
.;D;.;.
Vest4
0.24
MVP
0.072
ClinPred
0.16
T
GERP RS
4.6
Varity_R
0.064

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: rs534366697; hg19: chr2-74643242; COSMIC: COSV51762799; COSMIC: COSV51762799; API