rs373709012
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PM4_SupportingBP6BS1
The NM_001033855.3(DCLRE1C):โc.1385_1387delโ(p.Glu462del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000154 in 1,614,202 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: ๐ 0.00022 ( 0 hom., cov: 31)
Exomes ๐: 0.00015 ( 1 hom. )
Consequence
DCLRE1C
NM_001033855.3 inframe_deletion
NM_001033855.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.48
Genes affected
DCLRE1C (HGNC:17642): (DNA cross-link repair 1C) This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The encoded protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins. The protein also functions in the regulation of the cell cycle in response to DNA damage. Mutations in this gene can cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_001033855.3. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 10-14909099-ACTT-A is Benign according to our data. Variant chr10-14909099-ACTT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 430113.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000217 (33/152330) while in subpopulation EAS AF= 0.00154 (8/5186). AF 95% confidence interval is 0.000767. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCLRE1C | NM_001033855.3 | c.1385_1387del | p.Glu462del | inframe_deletion | 14/14 | ENST00000378278.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCLRE1C | ENST00000378278.7 | c.1385_1387del | p.Glu462del | inframe_deletion | 14/14 | 1 | NM_001033855.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152212Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
33
AN:
152212
Hom.:
Cov.:
31
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:
GnomAD3 exomes AF: 0.000330 AC: 83AN: 251224Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135764
GnomAD3 exomes
AF:
AC:
83
AN:
251224
Hom.:
AF XY:
AC XY:
41
AN XY:
135764
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000148 AC: 216AN: 1461872Hom.: 1 AF XY: 0.000153 AC XY: 111AN XY: 727238
GnomAD4 exome
AF:
AC:
216
AN:
1461872
Hom.:
AF XY:
AC XY:
111
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152330Hom.: 0 Cov.: 31 AF XY: 0.000228 AC XY: 17AN XY: 74478
GnomAD4 genome
?
AF:
AC:
33
AN:
152330
Hom.:
Cov.:
31
AF XY:
AC XY:
17
AN XY:
74478
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
6
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2017 | The c.1385_1387delAAG variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is observed in 26/8652 (0.301%) alleles from individuals of East Asian background in the ExAC dataset (Lek et al., 2016). The variant results in the in-frame deletion of Glutamic acid 462, a residue which is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
DCLRE1C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 10, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Severe combined immunodeficiency due to DCLRE1C deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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