chr2-99404587-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016316.4(REV1):​c.2902G>T​(p.Asp968Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. D968N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

REV1
NM_016316.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00
Variant links:
Genes affected
REV1 (HGNC:14060): (REV1 DNA directed polymerase) This gene encodes a protein with similarity to the S. cerevisiae mutagenesis protein Rev1. The Rev1 proteins contain a BRCT domain, which is important in protein-protein interactions. A suggested role for the human Rev1-like protein is as a scaffold that recruits DNA polymerases involved in translesion synthesis (TLS) of damaged DNA. [provided by RefSeq, Mar 2016]

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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=0.14500773).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
REV1NM_016316.4 linkc.2902G>T p.Asp968Tyr missense_variant Exon 18 of 23 ENST00000258428.8 NP_057400.1 Q9UBZ9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
REV1ENST00000258428.8 linkc.2902G>T p.Asp968Tyr missense_variant Exon 18 of 23 1 NM_016316.4 ENSP00000258428.3 Q9UBZ9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461766
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727186
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
16
DANN
Benign
0.77
DEOGEN2
Benign
0.038
.;T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.096
Sift
Uncertain
0.014
D;D
Sift4G
Uncertain
0.047
D;D
Polyphen
0.66
P;P
Vest4
0.40
MutPred
0.28
.;Loss of solvent accessibility (P = 0.0152);
MVP
0.43
MPC
0.24
ClinPred
0.45
T
GERP RS
3.6
Varity_R
0.17
gMVP
0.34

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: rs139233630; hg19: chr2-100021050; API