NM_001013628.3:c.835G>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001013628.3(DCAF12L2):c.835G>T(p.Ala279Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,210,626 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 25)
Exomes 𝑓: 0.0000046 ( 0 hom. 0 hem. )
Consequence
DCAF12L2
NM_001013628.3 missense
NM_001013628.3 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 1.14
Publications
0 publications found
Genes affected
DCAF12L2 (HGNC:32950): (DDB1 and CUL4 associated factor 12 like 2) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by Gly-His and Trp-Asp (GH-WD), which may facilitate formation of heterotrimeric or multi-protein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene appears to represent an intronless retrocopy of a related multi-exon gene located on chromosome 9. However, the CDS of this intronless gene remains intact, it is conserved in other mammalian species, it is known to be transcribed, and it is therefore thought to encode a functional protein. [provided by RefSeq, May 2010]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2220402).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000886 AC: 1AN: 112924Hom.: 0 Cov.: 25 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
112924
Hom.:
Cov.:
25
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000550 AC: 1AN: 181811 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
181811
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000455 AC: 5AN: 1097702Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 363082 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1097702
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
363082
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26402
American (AMR)
AF:
AC:
3
AN:
35183
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19322
East Asian (EAS)
AF:
AC:
0
AN:
30205
South Asian (SAS)
AF:
AC:
0
AN:
54058
European-Finnish (FIN)
AF:
AC:
0
AN:
40485
Middle Eastern (MID)
AF:
AC:
0
AN:
4131
European-Non Finnish (NFE)
AF:
AC:
1
AN:
841841
Other (OTH)
AF:
AC:
1
AN:
46075
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000886 AC: 1AN: 112924Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 35074 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
112924
Hom.:
Cov.:
25
AF XY:
AC XY:
0
AN XY:
35074
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31136
American (AMR)
AF:
AC:
1
AN:
10814
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2657
East Asian (EAS)
AF:
AC:
0
AN:
3548
South Asian (SAS)
AF:
AC:
0
AN:
2754
European-Finnish (FIN)
AF:
AC:
0
AN:
6267
Middle Eastern (MID)
AF:
AC:
0
AN:
238
European-Non Finnish (NFE)
AF:
AC:
0
AN:
53296
Other (OTH)
AF:
AC:
0
AN:
1527
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Apr 14, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.835G>T (p.A279S) alteration is located in exon 1 (coding exon 1) of the DCAF12L2 gene. This alteration results from a G to T substitution at nucleotide position 835, causing the alanine (A) at amino acid position 279 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of disorder (P = 0.0387);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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