chrX-126164544-G-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001013628.3(DCAF12L2):c.1381C>G(p.Leu461Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,207,514 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )
Consequence
DCAF12L2
NM_001013628.3 missense
NM_001013628.3 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 7.58
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000888 AC: 1AN: 112650Hom.: 0 Cov.: 24 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
112650
Hom.:
Cov.:
24
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:
GnomAD4 exome AF: 0.00000183 AC: 2AN: 1094864Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 1AN XY: 360810 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1094864
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
360810
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26356
American (AMR)
AF:
AC:
0
AN:
34926
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19112
East Asian (EAS)
AF:
AC:
0
AN:
30186
South Asian (SAS)
AF:
AC:
0
AN:
53590
European-Finnish (FIN)
AF:
AC:
0
AN:
40445
Middle Eastern (MID)
AF:
AC:
0
AN:
3771
European-Non Finnish (NFE)
AF:
AC:
2
AN:
840585
Other (OTH)
AF:
AC:
0
AN:
45893
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000888 AC: 1AN: 112650Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34798 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
112650
Hom.:
Cov.:
24
AF XY:
AC XY:
0
AN XY:
34798
show subpopulations
African (AFR)
AF:
AC:
1
AN:
31007
American (AMR)
AF:
AC:
0
AN:
10746
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2659
East Asian (EAS)
AF:
AC:
0
AN:
3563
South Asian (SAS)
AF:
AC:
0
AN:
2747
European-Finnish (FIN)
AF:
AC:
0
AN:
6194
Middle Eastern (MID)
AF:
AC:
0
AN:
239
European-Non Finnish (NFE)
AF:
AC:
0
AN:
53288
Other (OTH)
AF:
AC:
0
AN:
1523
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
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
Mar 19, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.1381C>G (p.L461V) alteration is located in exon 1 (coding exon 1) of the DCAF12L2 gene. This alteration results from a C to G substitution at nucleotide position 1381, causing the leucine (L) at amino acid position 461 to be replaced by a valine (V). 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
Uncertain
D
MetaRNN
Uncertain
D
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 phosphorylation at Y458 (P = 0.1664);
MVP
ClinPred
D
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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